Updates with CAR T Cells
Advances in the understanding of basic immunology have ushered in two major approaches for cancer therapy over the past 10 years. The first is checkpoint therapy to augment the function of the natural immune system. The second uses the emerging discipline of synthetic biology and the tools of molecular biology and genome engineering to create new forms of engineered cells with enhanced functionalities. The emergence of synthetic biology approaches for cellular engineering provides a broadly expanded set of tools for programming immune cells for enhanced function. Barriers to therapy of solid tumors will be discussed.
Prof. Carl H. June, Richard W. Vague Professor, Immunotherapy Director, Center for Cellular Immunotherapies, Director, Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Perelman School of Medicine

Genetically Enhanced T Cell Immunotherapies: From Academic Innovation to Industry Translation
Since the 1990’s, we have conducted clinical trials of gene modified T cells. Gene editing has created T cells resistant to HIV infection. Chimeric antigen receptor (CAR) T cells targeting CD19 on B cells leukemias and lymphomas have induced durable complete responses in patients who are relapsed or refractory to all other available treatments. New designs for genetically modified T cells include switches and potency enhancements that will be required for targeting solid tumors. In one such approach, multiplex gene editing was accompanied by lentiviral transduction of a T Cell Receptor against the cancer antigen NY-ESO-1. The first use of CRISPR in the US in humans demonstrated that multiplex human genome engineering is safe and feasible. Translation of these technologies from research bench to clinical application requires knowledge of the critical quality attributes of the engineered cell product and acceptable limits. The road forward for wide patient access to engineered cellular therapies depends not only on scientific progress in targeting, gene modification and cellular manipulation methods, but also on meeting automation, engineering, clinical site onboarding, and health policy challenges.
Prof. Bruce Levine, Barbara and Edward Netter Professor in Cancer Gene Therapy, Founding Director of the Clinical Cell and Vaccine Production Facility (CVPF) in the Department of Pathology and Laboratory Medicine and the Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania

CAR-T Cell Therapy in Autoimmune Diseases
- Principles of CAR T cell therapy and rationale for SLE treatment
- Efficiency and safety in Lupus
- Research agenda
- Understand current unmet needs in treatment of autoimmune disease
- Discuss the potential of CAR T cell therapy in autoimmune diseases
- Present the key datasets on CAR T cell therapy in autoimmune disease
Prof. Georg A. Schett , Professor of Internal Medicine, Head of Department, Department of Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany ( FAU )

Driving New CAR T Cells
- Multi-targeted CAR T cells in hematologic malignancies
- CAR-T in solid tumors, with focus on GBM – mechanisms of efficacy and resistance and activity in non-clinical and clinical testing
- New gene editing strategies to improve CAR-T cells
Prof. Marcela Maus, Director of Cellular Immunotherapy Program, The Krantz Family Center for Cancer Research, MGH Cancer Center, Paula O’Keefe Chair in Oncology, Professor of Medicine, Harvard Medical School

Current Advances and Challenges in Engineered Cell Therapy for Leukemia and Red Cell Disorders: from CAR T to CRISPR
- Current status of CAR T therapy for relapsed/refractory ALL
- Updates in CAR T toxicity management
- Alternative targets beyond CD19
- Engineered stem cell therapies for thalassemia and sickle cell disease
- Approval of Casgevy in the US for red cell disorder
Prof. Stephan Grupp, Novotny Professor of Pediatrics, Co-Lead, Pediatric Program, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine
Section Chief, Cellular Therapy and Transplant, Division of Oncology, Director, Susan P. and Stephen S. Kelly Center for Cancer Immunotherapy, Medical Director, Cell and Gene Therapy Lab, Children's Hospital of Philadelphia

The Future of Human Genome Editing: A Regulatory Perspective
- Status of gene therapy and genome editing
- Regulatory considerations for genome editing
- Regulatory guidance for genome editing
- Facilitating product development
Abstract: Genome editing offers tremendous promise for the treatment of disease. The US FDA understands that we need to re-evaluate and modernize our approach to the unique challenges of genome editing while also ensuring the resulting therapies are both safe and effective. The FDA is taking steps to facilitate more efficient genome editing product development. For example, the FDA will encourage the use of biomarkers as surrogate endpoints to help facilitate the accelerated approval of gene therapies for serious or life-threatening conditions, such as lysosomal storage disorders and neurodegenerative diseases affecting very small numbers of individuals. FDA is also running a pilot program to attempt to further accelerate the pace of development of therapeutics for very small populations with very high medical need. This pilot for rare pediatric genetic diseases will allow ongoing informal interactions during development of the product. Finally, while countries around the world have their own regulatory authorities, there are not uniform global quality safety standard for the evaluation and regulation of cell and gene therapy products. The FDA supports work toward global regulatory convergence and, ultimately, global harmonization of regulations for these products.
Dr. Peter Marks, Former Director, Center for Biologics Evaluation and Research, U.S Food and Drug Administration ( U.S FDA, CBER )

Nanobodies as Emerging Antibody and Cell Therapeutics for Cancer and Viral Infections
The emergence of nanobody technology has provided new hope for antibody and cell based drug development. Our laboratory at the U.S. National Cancer Institute at the NIH has constructed large nanobody phage display libraries derived from the VHH and VNAR single domains of dromedary camels and nurse sharks, respectively. In my talk, I will present recent examples of CAR-T cells based on our nanobodies targeting glypican-1 (GPC1) and B7-H3 (CD276) for the treatment of pancreatic cancer and pediatric cancers. We have also identified nanobodies capable of neutralizing SARS-CoV-2 and the Lassa virus. I will also discuss the structure and functional features of these nanobodies and CAR-T cells as innovative antibody and cell therapeutics.
Prof. Mitchell Ho, Senior Investigator, Head, Antibody Therapy Section, Deputy Chief, Laboratory of Molecular Biology, Director, Antibody Engineering Program, National Cancer Institute, NIH

Clinical Development of CAR T cell Therapy and Next Generation CAR T cells
- Define the concept of CAR T cell therapy for cancer
- Summarize clinical outcomes of CAR T cell trials
- Recognize barriers to CAR T therapy of cancer and highlight novel approaches to overcome these barriers
- Recognize novel CAR T cell designs utilized to optimize anti-cancer efficacy of this novel approach as well as how these armored CAR T cell designs may bridge the gap from liquid to solid tumors
Prof. Renier Brentjens, Deputy Director, Chair, Department of Medicine, The Katherine Anne Gioia Endowed Chair in Cancer Medicine, Roswell Park Comprehensive Cancer Center

Therapeutic Application of Human 3D Brain Organoids: Opportunities and Challenges
Brain organoids are 3D tissue cultures that resemble cell type diversity, tissue architecture and developmental trajectory of the native human brain tissues. Rapid advances in the stem cell technologies have led to human pluripotent stem cell-derived brain organoids that mimic the development and properties of different regions of the developing human brain. In parallel, brain organoids have been generated from patient surgical tissues, such as glioblastoma, that can maintain inter- and intra-tumor heterogeneity as well as the tumor microenvironment. I will review recent development of brain organoid technologies and provide examples for therapeutic applications of these human stem cell-derived brain organoids, such as applications during the past two global pandemics (Zika virus and SARS-Cov2). I will also discuss technologies of tumor organoids and their applications in the personized medicine. Finally, I will discuss challenges ahead.
Prof. Hongjun Song, Perelman Professor of Neuroscience, University of Pennsylvania

Glypicans as Emerging CAR-T Therapeutic Targets in Solid Tumors
The emergence of CAR-T cell therapy has provided renewed hope for many patients with B-cell malignancies. However, while CAR-T cells can safely target and destroy lymphoma and leukemia cells without harming other organs in the body, researchers have struggled to identify tumor-specific proteins that can be used in CAR-T cell therapy to target solid cancers without harming healthy organs in the process. In the past 15 years, we have investigated a family of such proteins called glypicans. Glypican-3 (GPC3) and GPC2 are highly expressed in hepatocellular carcinoma and neuroblastoma. More recently, we began to validate GPC1 as a target of CAR-T cell therapy in pancreatic cancer. The update about characterizing these glypicans as CAR-T targets in solid tumors will be presented. The engineering of more potent CAR-T cells using nanobody and protein engineering technologies will also be discussed.
Prof. Mitchell Ho, Senior Investigator, Deputy Director, the Laboratory of Molecular biology; Director, Antibody Engineering Program, National Cancer Institute, NIH.

SynNK Cells: beyond CAR-T Cells
Abstract: Natural killer (NK) cells are the first line against tumor with inherited innate receptors with an array of activating and inhibiting surface molecules to recognize the ligands on tumor and finally to activate NK cells for eliminating tumor. Comparing with “CAR”, an artificial receptor using antibody targeting associated antigen on tumor surface, NK receptors (NKR) and their ligands (NKR-Ls) are more valuable always-standing storehouse of surface targets for NKR as tumor-sensors or NKR-Ls as CARs. Though CAR-T become practical in clinic settings, NKR-NK cells, as effector cells, need pay more attention since advantages of NK cells over T cells, such as NK cells express many naturally-holding anti-tumor receptors in addition to modified CAR/NKR. Importantly, we could not stay at the stage of modification of NK cells only with tumor-sensor CAR or NKR, we need make a more intelligent NK cells with multiple functions to combat complicated “sly” tumor. So, synthetic immunology becomes an ideal tool to produce synthetic NK cells (SynNK) with Logic Gates to precise discriminate tumor from normal tissue, and Basic Circuit to prevent exhaustion, ageing and rejection, and to improve tumor-infiltrating and in situ amplification of NK cells, and so on
Prof. Zhigang Tian, Professor & Director, Institute of Immunology, School of Life Sciences and Medicine, University of Science & Technology of China

Innovative R&D and the Commercialization Road of CAR-T Cell Therapy for the Treatment of B-Cell Acute Lymphoblastic Leukemia
- Epidemiology, Treatment, and Great Umet Clinical Needs of B-ALL
- CAR-T Cell Therapy for the Treatment of B-Cell Acute Lymphoblastic Leukemia in global scale
- The Innovative R&D Road of Inaticabtagene Autoleucel Injection (CNCT19), a Chinese CAR-T Cell Therapy Product
Dr. Lyu Lulu, Chief Executive Officer,Juventas Cell Therapy

运用神经再生型基因疗法治疗退行性疾病
Dr. Gong Chen, Founder, NeuExcell Therapeutics
Professor, Director of Brain Repair Center,GHM Institute of CNS Regeneration, Jinan University

Treatment of neurodegenerative diseases with AAV & its CMC
Abstract: In situ cell reprogramming offers the hope of a regenerative therapeutic approach to numerous neurodegenerative diseases. Using AAVs to deliver reprogramming factors to glial cells can result in the transdifferentiation of these cells into neurons and the replenishment of specific neuronal cell populations lost in a given disorder.
In a chemically induced non-human primate model of PD, treatment with AAV-GM101 has led to improved motor behavior, increased dopamine concentration in the CSF, and enhanced dopamine signal within the striatum as measured by PET-CT. To achieve such significant improvement, the quality of AAV is critical, we’ll also discuss the chemistry, manufacturing and controls (CMC) of AAV.
Dr. Jingmin Zhou, Co-Founder & CEO, Genemagic Biosciences

Challenges and Approaches of Comparability Study in Autologous CAR-T Cell Therapy
Abstract: Autologous CAR-T cell therapy is featured with personal, living drug in vitro and in vivo, sterile, and complex characteristics, nevertheless, as drug, changes in materials, process, equipment, method, and sometimes manufacturing site are unavoidable along product development, it is challenging to assess the risks of such changes, even more so to rationalize comparability of pre- and post-change.
This presentation focuses on explore the approaches of comparability study in autologous CAR-T cell therapy. The key points include:
1) Types of changes
2) Risk assessment of changes
3) Quality attribute study
4) Analytical comparability study
5) Non-clinical study, and
6) Clinical bridging
7) Regulatory consultation
Dr. James Wang, Chief Technology Officer, Juventas Cell Therapy

CMC and non-clinical studies of iPSC-derived cell drugs.
Abstract: Development of multiple iPSC-derived cell drugs is on the fast track around the globe. We at Nuwacell are investing in the utilization of iPSC-derived mesenchymal stromal cells, natural killer cells, dopaminergic neural progenitors, and pancreatic beta cells to treat human diseases. To make these cells on an industrial scale with controllable qualities, we’ve developed unique CMC for each cell product, including the clinical-grade iPSC itself. Thus far, two of our products had received regulatory clearances into Phase I clinical trials in China.
- CMC of clinical-grade iPSC;
- CMC and non-clinical studies of iPSC-derived MSC;
- CMC and non-clinical studies of iPSC-derived NK cells;
- CMC and non-clinical studies of iPSC-derived imDAP.
Dr. Ying Zhang, Chief Technology Officer,Nuwacell Biotechnologies

Challenges and solutions for CART treatment of solid tumors
Abstract: Despite impressive clinical efficacy of T cells engineered to express chimeric antigen receptors (CAR) for some hematological cancers, the current applications of CAR T cell therapy, especially for treating solid tumors, are limited by some major challenges, such as the lack of safe cancer specific targets, highly heterogeneities of the tumors and the tumor microenvironment (TME). To make breakthrough in treating solid tumors, strategies to solve all these challenges are required. We have developed a (CAR or TCR) T cell engineering strategy by incorporating a LACO-Stim molecule for the aim of enhancing engineered T cells’ abilities to counteract with TEM and, at the same time, orchestrating both innate and adaptive immunities against tumors of the patients. This synergistic combination effective CART therapy with tumor vaccine has been proved in pre-clinical syngeneic mouse tumor models and early clinical trials.
Prof. Yangbing Zhao, Chairman & Chief Scientific Officer, UTC Therapeutics

Overcoming the Challenge of T-cell Immunotherapy in Solid Tumors
Abstract: CAR T-cell therapy has been highly successful in treating hematological malignancies, and as a result, there is growing interest in testing this technology for solid tumors. However, the biology of solid tumors is more complex than that of hematological malignancies. There are two major obstacles in T cell immunotherapy for solid tumors: difficulty of engineered T cell-infiltration into solid tumors, and availability of ideal target antigens. At Eureka Therapeutics, we have developed proprietary technologies to address these challenges. Our ARTEMIS technology demonstrated enhanced T-cell infiltration into solid tumors, and our T Cell Receptor-mimic antibody (TCRm) platform broadens the range of cancer[1]specific antigens that can be targeted, including those that are normally expressed intracellularly. We will present an update on our case studies using these technologies to treat liver cancer (HCC)
Dr. Hongbing Zhang, Vice President, Drug Discovery , Eureka Therapeutics

The application of human professional antigen receptors for the development of cell therapy.
Dr. Yi Li, Chairman and Chief Scientific Officer,TIOC Therapeutics

CD30 CAR-T cell therapy for relapsed/refractory CD30+ lymphoma patients
Abstract: CD30 is a membrane protein that is constitutively overexpressed on all stages of cells in classical Hodgkin lymphoma (HL) and anaplastic large-cell lymphoma (ALCL) with minimal/negligible expression on normal cells, rendering its an ideal target for CAR-T cell therapy to treat relapsed/refractory HL/ALCL patients. Thus, we designed a new third-generation anti-CD30 CAR, and conducted a pilot study of 15 r/r HL/ACLC patients to test the efficacy and safety of CD30 CAR-T cell therapy, resulting in 93.3% ORR, 86.6% CR, and none CRS/ICNAS/CRES over grade 3. Thereby, a Phase I registered clinical trial was carried out in a classic 3 + 3 dose escalation manner to further validate the safety and efficacy of CD30 CAR-T cell therapy. Expectedly, 100% ORR and 83.3% CR were observed in median/high doses, while none Grade ≥ 3 CRS was found in all 9 patients. Taken together, these clinical studies demonstrated CD30 CAR-T cell therapy as a safe and effective treatment for relapsed/refractory CD30+ lymphoma patients
Dr. Tony Zhang, Chairman of the Board, President, Wuhan Bio-Raid Biotech

Immune Checkpoints in Cancer Therapy
Abstract: Checkpoint inhibiting drugs targeting the PD1 pathway represent one of the most encouraging new therapeutics for cancer. Millions of cancer patients have benefited from using checkpoint inhibitors since their first approval in 2014 by the US FDA. However, most cancer patients do not respond to PD1 pathway inhibitors and those who do eventually develop disease progression. Therefore, there is a strong unmet need to improve the efficacy of PD1 pathway inhibitors or to develop drugs targeting new immune checkpoint regulators. In this talk, Dr. Chen will discuss new developments in the field of immune checkpoint research and new opportunities for developing the next class of anti-cancer immunotherapeutic drugs, either used alone or in combination with engineered T cell therapies.
Prof. Youhai Chen,Chair Professor, Dean of Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology

Universal CAR-T Therapy for Hematological Malignancies
Abstract: Autologous lymphocytes from patients are used to manufacture CAR-T cell products. This “personalized therapy paradigm” has limitations in the large-scale production and timely application of CAR-T cell therapy. Universal CAR-T cells (UCAR-T) might help eliminate these drawbacks and become a promising breakthrough in tumor immunotherapy. The design of UCAR-T cells with TCR or HLA-A knocked out by gene-editing technology, such as Zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN) and CRISPR/Cas9 system, successfully generates host-friendly allogeneic CAR-T cells high quality, prompt availability, and widespread application for patients. Now some UCAR-T clinical trials have been applied in B cell derived hematological malignanices including CD19, CD22 and BCMA and achieved eminent efficacy. Current challenges in adapting CAR technology for T cell disease include fratricide, T cell aplasia, and product contamination. UCAR-T cells also achived great progress. In our center, CD7 targeted UCAR-T cells for CD7 positive malignanices achieved 82.2% overall response rate. Although the utilization of UCAR-T cells has exhibited dramatic achievements in hematological malignancies, several limitations still exist in consideration of safety and efficacy. Most of all, GVHD is one of the major challenges that hinders the broad application of UCAR-T cells, as the current techniques are still unable to knock out TCR completely. Moreover, multiple genetic editing processes increase the risks of gene mutations, clonal expansion and potential on-target off-tumor effects. Reduced proliferation and persistence of UCAR-T cells in patients have also been observed, with failure to generate memory subsets, and the mechanisms behind those are still obscure. Modifications are still needed in the future
Prof. He Huang, President, The first Affiliated Hospital, School of Medicine, Zhejiang University

Synergize Powers to Build the Future: The Development Road of Inaticabtagene Autoleucel Injection（CNCT19）, an Innovative CD19 CAR-T Cell Therapy Drug from China
Dr. Lulu Lyu, Chief Executive Officer, Juventas Cell Therapy

Research Progress of Gene Editing Technology in Cell Therapy
- Introduction to gene editing technology and CAR-T technology
- Development and preclinical evaluation of non-viral site-specific integrated CAR-T technology
- Clinical treatment of non-viral site-specific integration of CAR-T cells
Prof. Mingyao Liu, Founder, Chairman and Chief Scientist, BRL Medicine

Gene modified NK cells: From Natural Basis to Design for adaptation and Kill
Abstract：iPSC-derived therapies have great promise in the effective treatment of many human diseases, potentially providing curative medical solutions for a wide range of life-threatening diseases, including cancer. iPSC derived NK cells could be safer, faster to produce, easier for gene manipulation, and cheaper, prove to be promising immunotherapeutic candidates for treating cancer. Allife aims to provide unlimited number of standardized, off-the-shelf iNK cells in current GMP-compatible conditions. Our group also focus on NK cell potency upgrading. Based on the iPSC gene editing platform, iPSC derived NK cells are design to target the tumor site and adapt hostile tumor microenvironment, so they can work in situations where T cells falter. By shifting the balance between the signaling of inhibitory and activating receptors, we succeed to produce iPSC-NK cells with enhanced expansion, in vivo persistence and tumor killing capability
- Allife aims to provide unlimited number of standardized, off-the-shelf iNK cells in current GMP-compatible conditions.
- Gene modified iPSC-NK cells are design to target the tumor site and adapt hostile tumor microenvironment
- Allife has succeed to produce iPSC-NK cells with enhanced expansion, in vivo persistence and tumor killing capability
Dr. Yuchun Gu, Chief Scientist and CEO, Allife Medicine

Development of innovative CAR-T technology platforms for to great unmet needs
Ÿ CAR-T industry’s bottlenecks and unmet needs.
Ÿ Strategies of innovative approaches to develop best-in-class CAR-T products.
Ÿ FasTCAR-T development
Ÿ Development of off-the-shelf CAR-T products
Dr. William (Wei) Cao, Founder, Chairman and Chief Executive Officer, Gracell Biotechnologies

The Latest Progress and Trend of Global CAR-T Cell Therapy for Solid Tumor
* CAR-T therapy has been successful in the treatment of some hematological malignancies, but the treatment of solid tumors faces greater challenges
* However, many latest development directions are exhibiting promising outcomes
* Among them, payload delivery has become the key to breaking the tumor immunosuppressive microenvironment
* In addition, many innovative combination strategies have produced encouraging results in the treatment of solid tumors with CAR-T
* At the same time, off-the-shelf cell therapy products for solid tumors are emerging
* Finally, the progress made by PersonGen in the development of CAR-T products for solid tumors is summarized.
Dr. Lin Yang, Founder and Chief Executive Officer, PersonGen BioTherapeutics

Integrating Cell Industry Chain Resources to Accelerate the R&D of Universal Cell Therapy Products
Abstract: After decades of accumulation and breakthroughs in cell therapy technology, more and more revolutionary therapeutic products have been developed. At present, major countries in the world have also issued corresponding policies to support the development and transformation of cell therapy products. Simultaneously, the continuous investment of international capital has promoted the rapid development of the cell therapy industry. With the reform and innovation of China's drug review and approval system in 2017, it has provided a historical opportunity for the development of China's cell therapy industry. The joint promotion of enterprises, talents, research institutions and capital markets in the field has promoted the rapid development and expansion of the domestic cell therapy industry in recent years. In 2021, the breakthrough of cell drugs in China's is achieved. At the same time, the future development of China's cell therapy industry is also facing many challenges, including materials, equipment, technology, funds, talents, and policies. How to better overcome these challenges is a question worthy of consideration and exploration.
Dr. Yu Zhang, Chief Executive Officer,VCANBIOPHARMA

CD30: a cancer target and a modulator for CAR-T product development
Abstract: CD30 is a member of TNFR family. CD30 is highly expressed in Hodgkin’s lymphoma and several other types of cancers. As well as in cells of immunologic diseases. It is also expressed in T cells upon activation, thus a CAR T cell product against CD30 may encounter fratricide issue during the manufacturing process. In this presentation, several strategies to overcome this challenge and results will be discussed. On the other hand, the interaction between CD30 and its cognate ligand, CD30L, may be immune suppressive, thus we also explored the possibility of enhancing CAR T activity by disrupting CD30-CD30L interaction. Based on these studies, we are developing CD30-focused platforms to generate CAR-T products for solid tumor and immune diseases.
Dr. Jinhua (Jim) Lu, Chief Scientific Officer, TriArm Therapeutics

How Innovative Base Editing System Leading Target Screening and In Vivo Study towards Diversified Therapeutic Indications
Abstract: Base editing provides the most advanced DNA and RNA editing treatment for variety of therapeutic targets with the best safety control and high efficacy. Unlike CRISPR and other "molecular scissors" gene editors which cause double strand breaks and massive off-target mutations, the transformer Base Editor (tBE) authentically patented from CorrectSequence Therapeutics has been applied in vitro and in vivo through different delivery systems to enable treatment of various diseases without these safety risks. The comparison between traditional CRISPR system and advanced base editing system will be addressed on fundamental technology platforms, medical applications, safety and editing efficiency. The applications of Base Editing and summary of global pipelines derived from base editing systems with diversified delivery systems will be presented.
Dr. Susan Mou, Chief Executive Officer, CorrectSequence Therapeutics

Exploration of new generation CAR-T therapy in solid tumors
Abstract: With many CAR-T cell drugs on marketing in China and the world, evidences of CAR-T cells in the treatment of recurrent and refractory hematopoietic malignancies have shown the unique clinical value. Whether it can be realized in solid tumors remains challenges. These challenges result mainly from the differences between solid tumors and hematological cancer in target, solid tumor-related immunosuppressive microenvironment, heterogeneity, etc. Facing these challenges, we have established a self-secreting nanobody CAR-T product platform based on the dual anti-tumor strategy of CAR-T targeting tumor antigen and changing tumor suppressive microenvironment. We can achieve targeting and killing tumor cell by CAR-T and meanwhile relieving immunosuppression in the tumor by continuously secreting nanobodies. The nanobodies are not only to relieve immunosuppression, but also protect CAR-T from tumor microenvironment immunosuppression, relieve the immunosuppression of tumor-infiltrating T cells (TIL) in vivo, promote TIL to target tumor cells with different markers to play the same anti-tumor role, and therefore alleviate the damage caused by tumor heterogeneity and immunosuppressive microenvironment.
Dr. Yan Sun, Co-Founder and Group COO, Shanghai Cell Therapy Group

CD7 CAR-T Cell therapy for T-Cell malignancies
Abstract: CAR T-cell therapies are urgently needed for T-cell malignancies, because of the dismal outcomes associated with conventional treatment for T-cell leukemia and lymphoma. However, a major obstacle to the development of effective CAR T-cell therapy for T-cell malignancies is that targets selected for treatment are mostly the lineage receptors for T-cells, which may cause difficulty for CAR T-cell manufacturing due to fratricide.
In this presentation, current CD7 CAR T-cell therapies for T cell malignancies will be reviewed. Several clinical stage CD7 targeting CAR T- cell therapies will be presented, including the choice of CD7 binding domains, signal stimulation domains, as well as several different strategies for preventing fratricide. Their respective clinical outcomes will also compared. Finally, our world leading IntraBlockTM CD7 CAR T-cell technology, which has achieved one of the ten greatest advances in Chinese Hematology in 2021, will be presented.
Dr. Alex Chang, Founder, Shanghai Yake Biotechnology

Cutting Edge Gene Therapies Need High Quality of AAVs Manufactured from Promising Platforms
Abstract: In vivo Glia-to-Neuron cell reprogramming is a cutting-edge gene therapeutical method to cure patients with neurodegenerative disorders, AAV is the most popular vehicle to deliver the functional modalities to the central nervous system, and the quality of GMP grade AAV vectors play critical roles. This presentation will focus on the manufacturing challenges of GMP grade AAV vectors.
Dr. Jing-min Zhou, Co-Founder and Chief Executive Officer, Genemagic Biosciences

Development of rAAV Gene Therapy Products in Hemophilia -- ZS801/ZS802 Development Story
- FVIII and FIX with enhanced activity
- Liver specific promoter with small size
- Serotype suitable for more patients
Dr. Biao Dong, Chief Executive Officer, Sichuan Real & Best Biotech

Engineered Human Pluripotent Stem Cell-Derived Natural Killer Cells
Abstract:Human pluripotent stem cells provide a key resource for cellular immunotherapies. Our group pioneered studies to demonstrate efficient production of natural killer (NK) cells can be efficiently derived from both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). These cells can be routinely genetically engineered to derive immune cells with improved anti-tumor activity. Specifically, hESCs and iPSCs serve as a platform to express chimeric antigen receptors and other modifications to enhance anti-tumor activity. Importantly, hESC/iPSC-derived NK cells can be expanded to clinical scale in current GMP-compatible conditions. Since NK cells function as allogeneic cells, this strategy enables use of hESC/iPSC-derived NK cells as an “off-the-shelf”targeted cellular immunotherapy against refractory malignancies. Our group has also initiated studies to do whole genome CRISPR/Cas9-mediated screening of different tumor cell types to identify novel regulators of NK cell activity
Dr. Dan S. Kaufman, Professor, Dept. of Medicine, Director of Cell Therapy Program,University of California San Diego Health,Co-Founder; Board Member and Chief Scientific Officer, Shoreline Biosciences

Engineered T Cell Immunotherapies Using Synthetic Immunoreceptors and Cytokine Systems
Dr. Michael C. Milone, Associate Professor of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Scientific Co-Founder and Co-Chair of the Scientific Advisory Board, Cabaletta Bio and Verismo Therapeutics

Technological progress in generation, maintenance, engineering and differentiation of pluripotent stem cells
After more than 10 years since the first human iPS cells were reported, stem cell technology is being used to create new medical therapies. At CiRA Foundation we strive for continuous improvement of all aspects of the iPS cells manufacturing and act as a bridge for the transfer of iPS cell technology from the academia to the biomedical industry.
We are working on the projects aimed at providing cells for both, allogeneic and autologous applications. It becomes clear that to reliably provide clinical-grade cells, required to be manufactured with adherence to cGMP regulations, our process development should proceed toward automation and optimization of the protocols. To highlight the technological progress in the stem cells field, I would like to present some of our work.
For the large-scale expansion of iPS cells, we are evaluating automated closed culture platforms, the CliniMACS Prodigy Adherent Cell Culture System (Miltenyi Biotec) with CellSTACK Chambers (Corning) and Quantum Cell Expansion System (Terumo BCT).
One of the challenges in the manufacturing of genetically engineered iPS cells is single-cell cloning. I will show our progress in the culture protocol optimizations and single cell dispensing experiments results with UP.SIGHT instrument (Cellink/Cytena).
Finally, I will discuss the single cell imaging and manipulation capabilities of the CellCelector platform (ALS Automated Lab Solutions) in combination with Elplasia nanowell plates (Corning) and SIEVEWELL slides (Tokyo Ohka Kogyo).
- large-scale iPSC expansion
- single cell cloning
- automation
Dr. Rafal Krol, Principal Investigator, Research and Development Center, Kyoto University, CiRA Foundation

From AAV gene therapy to in vivo genome editing: Developing novel therapies for OTC deficiency
Dr. Lili Wang, Research Director, Translational Research and Gene Editing, Research Associate Professor, Department of Medicine, Translational Research, Gene Therapy Program, Perelman School of Medicine, University of Pennsylvania

Developing Neuroregenerative Gene therapy to Treat Neurodegenerative Disorders
Dr. Gong Chen, Founder, NeuExcell Therapeutics, Professor, Director of Brain Repair Center, GHM Institute of CNS Regeneration, Jinan University

Ex vivo gene editing for the treatment of hematopoietic inherited diseases
Abstract: Advanced gene and cell therapies for the treatment of genetic diseases is a growing field thanks to the new gene editing tools available. Engineered endonucleases, such as CRISPR/Cas9 system, allow the generation of very precise sequence specific genetic modifications. Gene editing in the presence of therapeutic DNA template has opened the possibility of site-specific gene therapy, avoiding potential risks of insertional oncogenesis. In this regard, we have developed a clinically applicable strategy for the site-specific gene therapy of the PKLR locus, in which, mutations induce a type of hemolytic anemia called Pyruvate Kinase Deficiency. We combined CRISPR/Cas9 system with rAAVs for donor delivery of a codon-optimized PKLR cDNA to build an efficient, safe and clinically applicable system to knock-in therapeutic sequences at the translation start site in human hematopoietic progenitors (HSPCs). Edited HPSCs efficiently reconstituted human hematopoiesis in immunodeficient mice. Erythroid cells derived from edited PKD-HSPCs restored PKD erythropoiesis after gene editing. Overall, gene editing allows an integrated for the development of safe gene therapy approaches, as the definitive cure of those devastating rare diseases with unmet treatment.
Dr. Jose-Carlos Segovia, Co-Founder and Chief Scientific Officer, WuXi CorrGene

AAV Gene Therapy for Retinal Channelopathies: Strategies for CNGA1mutation-induced RP49
Abstract: As the advance of the understanding on the genetic basis for inherited retinal dystrophy, related AAV gene therapy has got significant progress in recent years. Many AAV and related ophthalmic programs have come into clinical trials, one case has been approved by US FDA (Spark’s Luxturna). However, recent announcement about the failure of several ophthalmic gene therapy, i.e. two Biogen’s Phase II/III gene therapy clinical studies in inherited retinal diseases last year bring some challenges, they are 1. Choroideremia (timrepigene emparvovec, BIIB111/AAV2-REP1) and 2. X-linked retinitis pigmentosa (RP) (XLRP, Cotoretigene toliparvovec, BIIB112) phase II/III gene therapy (called XIRIUS), it suggests that AAV gene therapy is not a simple gene augmentation and CMC issue. Here, we exhibited our pre-clinical results on CNGA1 gene therapy for RP49. First of all, we cloned and studied the normal functions of CNGA1 channel and then, we created a knockout (KO) mice associated with CNGA1 to match the human RP disease. The retina of these CNGA1 KO animals was then characterized to assess the relationship between the genotype and phenotype of retinal disease that affected patients. Following the identification patient population and the development of techniques (AAV or others) for the viral gene transduction of retinal cells, we delivered a copy of the normal CNGA1 gene into the retinal sites where the mutated genes exist via subretinal injection. When this was performed in animal models of monogenic diseases, which was at an early stage of retinal degeneration while the affected cells remained viable, gene augmentation to correct the structural and functional lesions characteristic of the specific diseases in the areas of the retina were successfully conducted.
Dr. Jay ( Ji-Ye ) Wei, Chairman and CEO, ViewGene Therapeutics

Considerations towards Development of In Vivo Gene Therapies
- In vivo Gene Therapy: key principles and major cmc challenges
- A development strategy to maximize flexibility and success of clinical programs
- Understanding the linkage between CMC and clinical outcomes, risk based approach to the determination of the control system
Dr. Markus Haindl, Global Head Gene Therapy Technical Development, Pharma Technical Operations Cell and Gene Therapy, Roche

Development and qualification of a NGS assay for control of vector genome integrity of an AAV9 drug product
Abstract & Bullet Points: Recombinant adeno-associated viruses (rAAV) are widely used in the gene therapies. Rigorous qualify control (QC) tests are required to control the rAAV products safety and efficacy. High throughput next-generation sequencing (NGS) technology is a powerful tool for characterizing rAAV drug products. We will present a case study on development and qualification of an NGS assay for control of vector genome integrity of a commercial AAV9 drug product.
Dr. Huimin Helen Tao,Principal Scientist, Analytical Development,Novartis Gene Therapies

Gene Therapies Viral Vector Manufacturing; Plasmid Production and Collaboration Considerations
- What is the major challenges in GCT CMC development and manufacturing in China?
- As a startup in GCT, what is our strategy to deal with the CMC issue? What is our collaboration
- Consideration towards vector/plasmid manufacturing?
Dr. Nova(Xinxing) Liu, General Manager, Shanghai Refreshgene Therapeutics

Cell Therapeutics a Complex Manufacturing Process
Abstract: Gene and Cell Therapy gaining more and more interest in efficient personalized precision medicine. From a manufacturing aspect cell therapeutics are fairly demanding in requiring chemical gene synthesis, plasmid DNA fermentation and purification, viral vector design and production via mammalian cell cultures such as HEK 293 cells, isolation of human T-cells from the patient of allogenic T-cells, propagation of the T-cells and transfection with the viral vector carrying the gene of interest for a ligand on the T-cell surface targeting the T-cell to the tumor cell to express their cytotoxic effect.
- Microbial plasmid DNA manufacturing
- Viral vector manufacturing
- Cell therapeutic manufacturing
- Fill & Finish
- End-to-End service provider
Dr. Rolf G. Werner, Professor, Industrial Biotechnology, University of Tubingen

Development of the Next Generation Cell Therapy via iPSC-CAR-NK
Abstract: Presentation of Neukio innovative approaches in generating gene-edited iPSC platform and multiple assets with solid tumor targeting CARs, and in developing robust CMC process for iPSC differentiation into NKs and expansion. The goal of Neukio is to develop the next generation immune cell therapies that are allogenic in nature, amendable for large scale production from clonal master/working cell banks compliant to GMP regulations, and with potentials to treat solid tumor patients.
Dr. Richard Wang, Founder, Chairman and Chief Executive Officer, Neukio Biotherapeutics

Gene modified NK cells: From Natural Basis to Design for adaptation and Kill
Abstract: iPSC-derived therapies have great promise in the effective treatment of many human diseases, potentially providing curative medical solutions for a wide range of life-threatening diseases, including cancer. iPSC derived NK cells could be safer, faster to produce, easier for gene manipulation, and cheaper, prove to be promising immunotherapeutic candidates for treating cancer. Allife aims to provide unlimited number of standardized, off-the-shelf iNK cells in current GMP-compatible conditions. Our group also focus on NK cell potency upgrading. Based on the iPSC gene editing platform, iPSC derived NK cells are design to target the tumor site and adapt hostile tumor microenvironment, so they can work in situations where T cells falter. By shifting the balance between the signaling of inhibitory and activating receptors, we succeed to produce iPSC-NK cells with enhanced expansion, in vivo persistence and tumor killing capability
Dr. Yuchun Gu, Founder and Chief Scientific Officer, Allife Medicine

One Platform Endless Pipelines: CAR-NK cells from engineered pluripotent stem cells with 3-D platform technology
Abstract: Clinical success of adoptive cell therapy with chimeric antigen receptor (CAR) T cells for treating hematological malignancies has revolutionized the field of cellular immunotherapy. However, critical to the success of CAR-engineered immune effector cell therapies will be the industrialization----converting the technologies into universal and cost-effective therapies for a large number of patients. Autologous CAR-T cell therapy faces two major obstacles: cell availability and high manufacturing cost, which makes it difficult for most patients. Donor-based CAR-T cells circumvent some of the above challenges, but still face the problem of graft versus host disease caused by allogenic T cells. Natural killer (NK) cell is a specialized immune effector cell type that recognizes and kills targets without human leukocyte antigen (HLA) restriction and prior sensitization. CAR-NK cells do not cause graft versus host disease (GvHD) and can be obtained from unrelated donors as well as pluripotent stem cells (PSC), representing an ideal off-the-shelf therapeutics for all patients. HebeCell has developed a robust proprietary scalable 3D-platform technology for PSC expansion and feeder-free NK cell differentiation with superior scalability and consistency compared to traditional approaches. As gene editing and CAR-engineering can be performed in PSCs, the establishment of master PSC-CAR cell bank targeting indication-specific antigens will provide inexhaustible cell sources for the manufacture of truly off-the-shelf and cost-effective CAR-NK cells for all patients of cancer, infectious and autoimmune diseases. The establishment of our proprietary 3D PSC-CAR-NK platform allows scalable, reproducible and efficient production of homogenous functional CAR-NK cells, which can be rapidly deployed worldwide for all patients.
- A proprietary scalable 3D iPS-NK manufacture platform with defined, serum-free and feeder-free conditions: pure and strong functional iPS-NK with CD8+ effector cell identity for immunotherapy, a truly viable unlimited/renewable source of immune cells with improved potency and simplified manufacture process
- Genetically manipulated and engineered with CARs at pluripotent stage: establishment of permanent, stable and clonal iPS-CAR lines for the manufacture of unlimited homogenous CAR-NK cells. Multiple master iPS-CAR cell banks targeting a variety of antigens for cancer, viral infection and autoimmune diseases: inexhaustible cell sources for all patients
- Development of next-generation 3D bioreactor platform and logistics: ultimate goal of making CAR-NK products affordable and available for ordinary patients and as easy to handle and use as conventional drugs
Dr. Shi-Jiang (John) Lu, President and Chief Executive Officer, HebeCell Corporation

Genetic medicine, Technology Innovation and Venture Opportunities
Dr. Chunlin Zhao, Chairman, Founder and CEO, Anlong Bio

iPSC-Derived Cell Therapies and Their Evaluation
- To generate platelets by direct differentiation from iPSCs
- To reprogram somatic cells into iPSCs after donor screening and select the best clone with the best capacity of differentiation
- To choose the right genomics editing tool to establish iPSCs and further edit them
- To build the evaluation system to assess the iPSCs and bank the library
- To align the quality control criteria for iPSC
Dr. Fangfang Zhu, Founder & CEO, HemaCell Therapeutics

Development of effective CAR T-cell therapies for T-cell malignancies
Abstract: CAR T-cell therapies are urgently needed for T-cell malignancies, because of the dismal outcomes associated with conventional T-cell leukemia and lymphoma treatment. However, a major obstacle to the development of effective CAR T-cell therapy for T-cell malignancies is that targets selected for treatment are mostly the lineage markers for T-cells, which may cause difficulty for CAR T-cell manufacturing due to fratricide. In this presentation, current CAR T-cell therapies for T cell malignancies will be reviewed. Several clinical stage CD7 targeting CAR T- cell therapies will be evaluated, including the choice of CD7 binding domains, signal stimulation domains, as well as different strategies for preventing fratricide. Their respective clinical outcomes will also explored. Finally, our world leading IntraBlockTM CD7 CAR T-cell technology, which has achieved one of the ten greatest advances in Chinese Hematology in 2021, will be presented.
Dr. Alex H. Chang, Founder and Chief Executive Officer, Yake Biotechnology

Regenerate Lung and Kidney using Adult Progenitor Cells : Curing the Uncurable
Abstract: Lung and kidney disorders including idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and end-stage renal diseases are amongst the leading causes of global mortality and emergency admissions. This is accompanied by a huge healthcare expenditure globally. This high resultant mortality coupled to high frequency and annual costs position repair of the organs at the forefront of stem cell-driven regenerative medicine approaches. Regend Therapeutics, founded in Shanghai since 2015, is providing state-of-the-art tissue-specific stem/progenitor cell-based solutions to develop lung and kidney repair R-Clone^TM platform in the creation of future therapeutic approaches.
Dr. Wei Zuo, Founder and Chairman, Regend Therapeutics

IND application strategies of CART products: from FDA to NMPA
Abstract: Chimeric antigen receptor T cell (CART) therapy is a promising therapeutic strategy against cancer and draws extensive attention from academia and industry. CART products are living drugs, bringing challenges for companies and regulatory agencies. Here the speaker will share his experiences in IND applications in both US and China, illustrate the main regulatory principles of CART products on both sides, and discuss the dos and don’ts in an IND application.
Bullet points:
- Regulatory principles of CART products: from FDA to NMPA
- The dos and don’ts in IND applications of CART products
- CART cell manufacturing from a regulatory perspective
Dr. Changfeng Zhang, Regulatory Affairs Director, Shanghai Pharmaceuticals Holding

Driving CAR-T/TCR-T-cell-based Cancer Immunotherapy to Solid Tumors
Abstract : Current CAR/TCR T cell therapies are limited majorly by the lack of cancer specific targets and the interference of tumor microenvironment (TME). Strategies to identify safe targets as well as safe ways to target some validated tumor associated antigens. An efficient T cell adoptive immunotherapy requires to make T cells not only specifically targeting cancers, such as by expressing CAR or TCR, but the T cells need to be further modified to avoid tumor microenvironment (TME) as well, such as introducing a dominant negative TGF-beta receptor, antibodies against inhibitory co-stimulator molecules, cytokines, switch receptors or knocking out inhibitory co-stimulator molecules in the T cells. Furthermore, gene editing technologies greatly facilitate the development of universal CAR T and universal TCR T cells as the off-the-shelf T cell products to treat cancers, which holds great promise in advancing the field of cancer immunotherapy.
- Safely targeting cancers is utmost important for developing an effective T cell therapy
- Overcoming TME is critically important for T cell therapy to solid tumors
- Gene editing can greatly facilitate the development of cancer immunotherapy
Prof. Yangbing Zhao , President & Chief Scientific Officer, UTC Therapeutics

Maximizing the Therapeutic Potential of CAR-T Cell Therapy Using CRISPR/Cas9 Gene-Editing Technologies
- Challenges and opportunities of CAR-T cell therapy for solid tumors
- Technical progress of CAR-T cell therapy
- CRISPR/Cas9 gene editing system for CAR-T therapy development
- Progress of our universal CAR-T product for solid tumors
Dr. Xiaoyun Shang , Chief Executive Officer, Suzhou T-Maximum Bio-tech

Genetically Modified oHSV with Biomarkers to Enable CAR-T/ADC/BiTE Combination Therapy
Abstract: ImmVira was founded as a biotechnology company focused on genetically modified oncolytic viruses ("OV") as potential cancer therapeutics. The company has developed science, technology and know-how to support ongoing research, development and commercialization of best in class oncolytic viruses on the OvPENS (OV+ Patent, Enabling, Novel & Safe) platform. OvPENS platform comprises of research, patents, gene-recombinant knowhow, manufacturing technology and commercialization analytics to develop next generation OVs that reach drug development targets including Potent, Enabling, Novel and Safe. The OvPENS team also made several novel drug discoveries with the target to enable CAR T-cell, ADC and BiTE effective on solid tumors using an OV based vector-receptor approach
Dr. Grace Zhou, Chairman and Chief Executive Officer, ImmVira

Leading the innovation of cell therapy by gene editing
-- The new generation of gene editing technology enabling infinite imagination
-- The cell therapy still needs breakthrough for satisfied efficiency
-- Gene editing makes cell therapy different in manufacturing and curative effect
With the revolutionary breakthroughs in gene editing technology, the CRISPR and base editing technology have been widely used in both research and clinical trial. Meanwhile, the adoptive cell transfer (ACT) technology such as CAR-T therapy has been well recognized as the new hope of cancer patients which has tremendous prospect and potential. Whereas, the CAR-T therapy still has some bottlenecks to be broken for further application in cancer especially solid tumor therapy. The classical manufacturing of CAR-T cells based on viral infection which could insert the CAR into the genome of T cells arbitrarily which increase the production cost and malignant transformation risk. And the obstacles in solid tumor therapy has an urgent needing for gene enhanced T cells. Thus, the combination of CAR-T therapy with gene editing are taken for granted. Now gene editing has been used in developing non-viral dependent CAR-T, off-the-shelf universal CAR-T and reinforced CAR-T cells for solid tumor which will widely broaden the patient access to CAR-T cells and benefit more and more cancer patients.
Prof. Liu Mingyao , Chairman & Chief Scientific Officer, Shanghai Bioray Laboratory ; Professor, East China Normal University

The Development Progress of IM19 CAR-T Cells in Relapsed or Refractory Non-Hodgkin Lymphoma
Dr. Ting He, Chief Executive Officer, ImmunoChina Pharmaceuticals

CART therapy regulation and IND application in China
Chimeric antigen receptor T cell (CART) therapy is a promising therapeutic strategy against cancer and gains extensive attentions from both academia and industry. CART products are living, self-replicating drugs, and thereby bring challenges for both companies and regulatory agencies. So, what are the unique features of CART products from a regulatory perspective? What are the similarities and differences in IND regulation between FDA and NMPA? To what orientation will CART regulation evolve to maximize the safety while maintaining flexibility? Here, the speaker will share his experiences in IND applications in both US and China, illustrate main regulatory principles of CART products in both sides, and discuss the do’s and don’ts in an IND application.
Bullet points:
l Regulatory principles of CART products: from FDA to NMPA
l The do’s and don’ts in IND applications of CART products
l CART cell manufacturing from a regulatory perspective
l The use of correlative sciences in CART IND applications
Dr. Changfeng Zhang, Associate Director, Dept of Cell Therapy, Livzon Biotech

TIL Therapeutics in Solid Tumor: Advantages, Challenges and Development Trends
- The advantages of TIL therapeutics for solid tumor
- The challenges in developing personal TILs drug
- The development trends of TIL therapeutics
Dr. Huajun Jin, Founder, CEO & CTO, Shanghai Gencells Therapeutics

Developing safe and effective T-cell therapies to treat solid tumors: ARTEMIS T-cell therapy targeting tumor specific antigens with enhanced tumor infiltration
Dr. Cheng Liu, Founder and CEO, Eureka Therapeutics

Building Clinical-grade Stem Cell Library for Developing off-the-shelf Cell Therapy Products in China
- Advance in cell therapy product development in China
- Building different clinical-grade stem cell bank and platform
- Examples of developing allogenic cell therapy products such as MSC for COVID-19
Dr. Yu Zhang, Senior Vice President and Chief Scientific Officer, VCANBIO Cell & Gene Engineering

Enhancing AAV Gene Therapy Efficiency
Abstract: AAV gene therapy has proven to be an effective long-term cure and has the potential to be applied to all kinds of diseases. However, drug development is hindered by relatively low efficiency, high side effects, high dose, high price and long manufacture time. For next generation AAV gene therapy, enhancing the efficiency can solve all these problems and should be the first step for every new therapy pipeline. At AAVnerGene, we strive to develop new technologies to enhance AAV gene therapy efficiency from vector design, process development, new capsid screening and gene expression regulation. Our proprietary platform, ATHENA (AAVnerGene’s Tissue-specific, Highly-transductive and Expressive New AAVs), combines library screening with AI-directed rational design to fast and effectively develop new AAV capsids for different target diseases. We are also developing new gene therapy cure for hemophilia A. Our patented FVIII has increased activity up to 40 fold than current FVIII in clinical trial. Combining the improved vector design, gene regulator and new capsid, the new drug will dramatically increase the efficiency and decrease the dose, which will solve the side effects, manufacture and high price problems, and bring affordable new option to the patients.
Dr. Daozhan Yu, President and Chief Executive Officer, AAVnerGene

Novel Proceeding about Targeting CD 30 CAR-T Therapy for Lymphoma
Abstract: CAR-T cells therapy has been demonstrated good tolerability and effects in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphomas (ALCL). However, most studies utilized the second-generation CARs with either CD28 or 4-1BB costimulatory domains resulting in unsatisfactory complete remission rate. Here, we designed a novel third-generation CAR against CD30 and investigated the efficacy and safety on CD30 positive relapsed or refractory lymphoma patients. We found that the anti-CD30 CAR-T cells specifically homing to the tumor with powerful anti-tumor activity in the tumor xenografts. We then conducted a pilot study to evaluate the safety and feasibility of anti-CD30 CAR-T cells which were infused simultaneously in 14 patients with r/r HL and ALCL. The third-generation anti-CD30 CAR-T cells had superior expansion and longer persistence, and the lentiviral copies could be detected after CAR-T infusion for half a year. Of Thirteen patients (92.9%) were successes responded and ten patients (71.4%) achieved complete remission (CR) for 12 months and also four patients remained in CR longer than two years in the patients (4/5) followed over two years. Our results showed that CRS occurred in eleven patients but was mild, only one patient developed CRS over 3 grade, and other 10 patients developed grade 1 or 2 CRS who did not require anti-IL6 therapy. Thus, anti-CD30 CAR-T cells is safety and effective for treating relapsed/ refractory HL and ALCL patients.
Dr. Tony Zhang, Chairman and Chief Executive Officer, Wuhan Bio-Raid Biotechnology

Solid Tumor CAR-T Barriers and Solutions
• Solid tumor quite different from hematologic malignancies
• Tumor microenvironment
• CAR-T design, traditional CAR, novel concept CAR, TCR-like
• Therapy combination
Dr. Enxiu Wang, Chief Executive Officer, Nanjing CART-MED

The Latest Advancement in T-cell-based Cancer Immunotherapy
Cancer is a leading cause of death worldwide. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. Chimeric antigen receptor (CAR)-T cells have achieved great success in treating hematological malignancies, while tumor infiltrating lymphocytes (TIL) and T cell receptor (TCR) -T cell-based immunotherapy have shown encouraging data for solid cancers. In this presentation, I will highlight the latest advancement in T-cell-based cancer immunotherapy based on TIL, TCR-T and CAR-T cells and discuss future directions and challenges in T cell-based cancer immunotherapy.
Dr. Mingjun Wang, Executive President, Shenzhen Institute for Innovation and Translational Medicine

Platform for Identification and Optimization of TCR for Shared Tumor Antigens in Large-Scale
Dr. Xingwang Xie, Founder & Chief Executive Officer, Corregene Biotechnology

Development of Safe and Potent CD19 CAR-T Cell Therapy in China targeting Hematological Malignancies
Abstract: CD19-targeted chimeric antigen receptor-T (CAR-T) cells with CD28 or 4-1BB (28z CAR-T and BBz CAR-T) have shown great promise to treat relapsed or refractory (r/r) B cell non-Hodgkin’s lymphoma (B-NHL). However, parallel comparison of their clinical outcomes has never been reported. This study investigated their efficacy and adverse events in B-NHL therapy. Six patients with r/r B-NHL were initially enrolled and infused with 28z or BBz CAR-T cells at a dose of 0.75–5x105/kg. These CAR-T cells showed similar antitumor efficacies, with a complete response (CR) rate of 67% within 3 months. BBz CAR-T was well tolerated. However, severe cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in the 28z CAR-T cohort, resulting in the termination of further evaluation of 28z CAR-T. Three more patients were enrolled to investigate BBz CAR-T cells in-depth at an escalated dose (1-106/kg). All cases achieved CR within 3 months, and only grade 1/2 adverse events occurred. This study suggests that 4-1BB is more beneficial for the clinical performance of CAR-T cells than CD28 in CD19-targeted B-NHL therapy, at least under our manufacturing process.
Dr. Ting He, Chief Executive Officer, ImmunoChina Pharmaceuticals

The Research and Proceedings of CAR-T for Treating the Acute myeloid leukemia (AML)
Dr. Jishuai Zhang, Chief Scientific Officer, The Pregene Biopharma Company

Surface Density of CAR Molecules Modulate the Kinetics of CAR-T Cells In Vivo
Dr. Jianqiang Li, Founder and Chief Scientific Officer, Hebei Senlang Biotech
Adjunct Professor, Second Hospital of Hebei Medical University

What can Flow Cytometry Do for CAR-T
• Flow cytometry can be helpful in CAR-T design and tocicity prediction
• Identify the quality of immune cells
• MRD detection after CAR-T
• Immune surveillance
• Cytokines by ELISA, detect more cytokines by FCM
Dr. Hui Wang, Deputy Director, Clinical Diagnostic Dept, Director, Flow Cytometry Lab , Lu Daopei Medical Group; Director, CEO, CMO, Synarc Research Laboratory (Beijing) Ltd

Precision TCR Redirected T Cell Immunity Treating Solid Tumour
• The Evolution of TCR-T
• XLifeSc 3rd Generation TCR-T
• Case Studies of TCR-T Drug Treatment for Solid Tumors
Dr. Yi Li, President and Chief Scientific Officer, Guangdong Xiangxue Life Sciences, Principal Investigator of Center for Infection & Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Principal Investigator, State Key Laboratory of Respiratory Disease

The Significance, Prospect, Risk Control of Fully Automated CAR T Cell Manufacturing
摘要(Summaries)：
1.免疫治疗的进展正在改善许多晚期恶性肿瘤患者的预后
2.CAR-T细胞能有现在的成就，归功于多学科的成功融合
3.高质量的临床级CAR-T细胞产品的可重复制造是CAR-T技术能够广泛应用的先决条件
4.CAR-T细胞产品制备中的全过程质控是必须具备的条件
5.全封闭、自动化的CAR-T细胞制备，成为该治疗模式广泛应用和最终商业化的优先选择
Dr. Min Wang, Chief Technology Officer, PersonGen BioTherapeutics

Cell & Gene Therapy Manufacturing from Concept to Patient
Abstract: The field of cell and gene therapy is transforming the way patients diagnosed with cancers or genetic diseases can be treated. These novel drug candidates provide drastically improved patient outcomes and, in some cases, can be curative. However, manufacturing of such medicines pose complex new challenges. Today, the cost of production still represents a major hurdle for clinical translation and commercialization of these potentially ground-breaking therapies. New technologies are needed to enable robust and cost-efficient manufacturing of high-quality medicines. While the therapeutic opportunities for patients are exciting, the stakes for patients and drug developers are high.
During this presentation we review:
- The key challenges of bringing a cell/gene therapy to market
- Establishing a roadmap from early stages to commercialization
- Platform technologies to achieve commercial viability
Dr. Hartmut Tintrup, Global Head of Business Development & Partnering, Cell & Gene Technologies Business Unit, Lonza

High-titer and scalable viral vector manufacturing through complete suspension LV and AAV production systems
Abstract: Recombinant lentivirus (LV) and adeno-associated virus (AAV) are critical components of cell and gene therapies, which show great promise for treatment of diseases from genetic disorders to cancer. There are increasing needs for high titer and scalable viral vector processes from research and development to manufacturing.
Thermo Fisher Scientific offers innovative complete suspension systems, LV-MAX and AAV-MAX, to support high-titer and scalable viral vector manufacturing.
Below are discussion points of LV-MAX and AAV-MAX systems
• Integrated components and processes in two systems
• High-title performance and scalable consistency
• Research-grade and GMP options
• Update of other GMP supports in cell and gene therapy workflow
Dr. Eddie Sun, Strategy Alliance Manager, GC & JP, Thermo Fisher Scientific

Parallel GMP Manufacturing to Develop Gene Therapies in Both the US and China
Dr. Jimmy Zhang, Founder, Chairman and CEO, AccuGen Group

Off-the-shelf” human blood manufacturing from pluripotent stem cells to mitigate donor blood shortages from infectious diseases
Abstract: Globally an estimated 112.5 million units of blood are collected for transfusion applications from blood donors. Unfortunately, since the COVID-19 pandemic, many nations like Singapore have had extreme depletion of bloodstocks, and loss of healthy donors. Alternatives to donated blood must be found to solve an escalating shortage of blood.
Continual advancements in the fields of lineage differentiation, bioprocessing and scale-up culture have brought closer the reality of using hiPSCs-differentiated cells for therapeutic applications and regenerative medicine. One such potential is the use of hiPSCs to generate O –ve universal RBCs for transfusion applications. However, unlike most cell therapies, generating RBCs for clinical application poses unique bioprocessing and manufacturing challenges. The need to generate 2 trillion RBCs for each transfusion unit of blood (equivalent to 300 ml of donated blood) requires the development of ultra-high density cultures of cells.
We demonstrate significant progress in solving the manufacturing challenge by:-
1. Implementing efficient reprogramming of hiPSC in suspension microcarrier cultures at the start of the process. Screening hundreds of clones and selecting dozens with both features of high expansion capability (greater than 10-fold) and differentiation to early hematopoietic lineage, positive for CD34 and CD43 markers (above 70%).
2. Initiating of the mesoderm differentiation in suspension culture and selection of clones with at least 20-fold expansion and production of T-bra and KDR +ve cells (>20% expression)
3. Simplifying differentiation with implementation of designs of experiments to use small molecules and reduced cytokine cocktails towards the erythroblast lineage. Screening a second stage for high expandability to erythroblasts, > 20,000 fold or more; while decreasing cost of goods by 10 fold.
4. Applying high intensity culture methods using ultrasound to concentrate erythroblast expansion to achieve greater than 25 million cells/ml in controlled bioreactor cultures.
5. Applying shortened, simplified enucleation protocol with inactivated OP9 co-cultures and screened plasma sources to drive enucleations rates up by 10 fold or more from 6% to 65%.
6. Characterisation of oxygen binding curves, haemaglobin expression, membrane fluidity and SEM images.
We present solutions to developing a bioreactor scalable-process for generating high-density cultures of functional O-ve universal RBCs from hiPSCs.
* Prof. Steve Oh, Institute Professor and Director, Stem Cell Group, Bioprocessing Technology Institute, A*STAR

Cell Therapy Bio-manufacturing and Cell Processing
Prof. Mickey Koh, Director Stem Cell Transplantation, St George's Hospital and Medical School, London, UK, Medical Director, Health Sciences Authority, Singapore

Towards Commercialization – Accomplish the Challenges of Cell and Gene Therapies
• Review how manufacturing processes can affect quality attributes of living drug products
• Considerations ofChina Business Heading process in the context of process transfer
• Assess industry collaboration strategies
Dr. Hermann Bohnenkamp, Vice President, Business Development APAC, Miltenyi Biotec
Dr. Silvio Weber, Head of the Industrial Process Development Team, Miltenyi Biotec

Automated Manufacturing of Chimeric Antigen Receptor T Cells
Abstract: The chimeric antigen receptor gene-modified T cells (CAR-T cells) technology has been proven clinically successful since 2010, especially targeting CD19 molecules in the treatment of refractory, relapsed B cell-derived malignancies in which the clinical efficacy has never been achieved by traditional tumor therapy strategies, and become the most attractive area in cancer immunotherapy. However, CAR-T cell technology has been experiencing huge challenges, including the expensive preparation and quality control costs for CAR-T cells and lacking clinically verified automated and closed technology. In another word, current mainstream technology hugely relies on highly skillful personnel that increases risk of contamination and production failure, and brings uncertainty for its industrialization. In this presentation, Dr. Yang will analyze the development trend based on his team’s effort in this area, and summarize how applying automated platform to CAR-T cell manufacturing will prompt CAR-T cell technology industrialization and lead to clinical success.
Dr. Lin Yang, Founder, Chairman and Chief Scientific Officer, PersonGen BioTherapeutics
Chairman & CEO, PersonGen-Anke Cellular Therapeutics