Editor's Note: The 11th Sino-French Hematology Academic Conference, organized by the Chinese Medical Doctor Association, recently took place in Tianjin, drawing hundreds of leading experts and scholars in the field of hematology from around the world. During the conference, Hematology Frontier invited Dr. He Huang from The First Affiliated Hospital, Zhejiang University School of Medicine and Dr. Didier Blaise from the Hematology Institute of Aix-Marseille University in France to engage in a dialogue on the challenges and opportunities in new cellular therapies for hematologic malignancies. Here are the key insights from their conversation.

Tracing the Development Trajectory of Cellular Therapy from a Sino-French Perspective

Dr. Didier Blaise: Cellular therapy is both an old and a new story. It is an “old story” because it began nearly 70 years ago with allogeneic transplantation. It’s important to remember this history, as we have learned a great deal over the past 30 years. This laid the foundation for the development of what we now call cellular therapy, including directed and targeted approaches, such as CAR-T cell therapy. Both approaches are crucial, and Professor Huang’s team has demonstrated that they can be successfully combined. In France and Europe, the use of both allogeneic transplantation and cellular therapy is increasing, especially with the growing number of elderly patients requiring such treatments. However, the situation in France differs from that in China, and to a lesser extent, from the U.S., as the level of academic development regarding new forms of CAR-T cell therapies is not the same.

Dr. He Huang: As Dr. Didier Blaise noted, cellular therapy and hematopoietic stem cell transplantation have been practiced globally for many years. CAR-T therapy, which involves genetically modifying T cells to treat diseases such as hematological malignancies, emerged around 15 years ago. Currently, there are approximately 12 commercial CAR-T products available in China and the U.S. In addition, numerous clinical trials are underway in China, the U.S., and Europe to develop new treatments aimed at improving efficacy, reducing toxicity, and benefiting more patients. The advancement of cellular therapy, stem cell transplantation, and CAR-T therapy requires extensive collaboration and knowledge exchange with global counterparts. For over 20 years, we have maintained close academic ties with the European Society for Blood and Marrow Transplantation (EBMT), which has facilitated progress in both clinical and research fields. Our close cooperation with European colleagues, as emphasized by Professor Blaise, is indeed valuable and encouraging.

Advancing Cellular Therapy: Pioneering Diversified Targets and Enhanced CAR-T Therapies

Dr. He Huang: Previously, the development of commercial CAR-T products mainly focused on CD19 and BCMA targets. However, considering the complexity and diversity of hematologic malignancies, which span various lineages such as T-lineage and myeloid cells, our top priority now is to explore and expand treatment targets. Moreover, cellular therapies show great potential in treating a wide range of diseases beyond traditional hematologic malignancies, including solid tumors and autoimmune diseases. Finding new therapeutic targets will undoubtedly benefit a broader patient population.

Additionally, due to the limited efficacy of commercial CAR-T products in lymphoma, where only about half of the patients achieve complete remission, we urgently need to develop more effective CAR-T therapies. This entails addressing key challenges such as gene editing and metabolic regulation to enhance treatment response and long-term survival rates.

Lastly, the development of universal CAR-T products is an attractive avenue for exploration. Currently, CAR-T therapy is highly individualized, involving a lengthy and costly manufacturing process that limits its clinical application. Therefore, developing a more economical and broadly applicable universal CAR-T therapy is essential for advancing and popularizing cellular therapy. China is actively partnering with domestic and international pharmaceutical companies to develop these novel cellular therapy products and usher in a new era of cellular treatments.

Dr. Didier Blaise: Our research team is focused on a specific area—aggressive lymphoma. Although the current number of patients treated is relatively limited compared to the overall oncology field’s needs, we have made steady progress in treating refractory cases. This progress owes much to the efforts of many international researchers, particularly Professor Huang’s team in China, whose outstanding achievements have allowed us to intervene earlier in the course of the disease and significantly improve treatment outcomes. However, continued exploration is necessary to gain new insights and drive advancements in the field.

The concept of universal therapies highlighted by Professor Huang is especially crucial, as it is the only way to implement first-line treatment for highly aggressive diseases. When treatment is delayed, the chances of curing the disease diminish significantly. Moreover, investigating diverse treatment targets is essential, and China’s work in this area has already shown remarkable results. The treatment of myeloid malignancies, which is more complex and challenging than that of lymphoid malignancies, remains a focus of future study and exploration. Despite the difficulties, it is an important and promising field.

Furthermore, China’s research initiatives show great promise in various fields, particularly cellular therapy for solid tumors. There is an urgent need for increased research efforts on highly aggressive diseases such as liver and pancreatic cancer. Additionally, autoimmune diseases, often overlooked, could also greatly benefit from cellular therapy.

From Exchange to Practice: International Collaboration Accelerates Innovation and Application of Cellular Therapy

Dr. He Huang: In the future, a variety of therapies will be widely applied in clinical practice, extending beyond hematology to a broad spectrum of diseases. Looking ahead, cellular therapy holds great potential for treating not only hematologic malignancies but also autoimmune diseases and solid tumors, opening new therapeutic chapters.

Moreover, while cellular therapy is a promising approach, its potential could be further unlocked through integration with other advanced treatment strategies, such as monoclonal antibodies and small-molecule targeted therapies. The synergistic effects of such multimodal treatments could significantly enhance clinical outcomes, bringing greater therapeutic benefits to patients.

Throughout this process, the importance of international collaboration cannot be overstated. Just as the close partnership with the EBMT has demonstrated in the field of stem cell transplantation, we hope to establish a broader international cooperation network in cellular therapy. We look forward to working with renowned experts like Dr. Didier Blaise, whose valuable guidance and advice will be instrumental in advancing the field.

Hand in Hand Across Borders: Future Prospects in Cellular Therapy

Dr. Didier Blaise: Professor Huang has outlined the potential of universal therapies and the exploration of new targets. These factors are crucial for accurately predicting and driving the next era of medical advancements. Unlike the early stages of cellular therapy, where toxicity management was the main concern, the core challenge now lies in identifying the specific treatment strategies for each patient and disease.

We are striving to reduce the relapse rate in patients. By implementing earlier interventions, we aim to solve the issue of non-responders, shifting the focus from refractory patients to addressing relapse. Collaboration across disciplines and teams is essential for exploring diverse treatment pathways. For example, sequential treatments and the combination with allogeneic transplantation, as demonstrated by Professor Huang’s team, offer valuable insights and guidance. These efforts illustrate the limitless possibilities in medical research and signal a bright future for cellular therapy.

Dr. He Huang: I completely agree with Professor Blaise’s viewpoint. Cellular therapy is still in its infancy, and its future looks bright. Beyond designing new targets and innovative therapies, the entire healthcare system’s construction is vital, including enhancing patient awareness, fostering collaboration among hospitals, governments, and pharmaceutical companies, and jointly promoting the development, approval, and clinical application of novel therapies. The broad understanding and acceptance of these new therapies are key to ensuring they genuinely benefit patients. Through joint efforts and persistent exploration, we can elevate the field of cellular therapy to higher levels and achieve significant progress in medical science and technology.

Dr. He Huang

• Qiushi Distinguished Professor, Zhejiang University
• Chief Scientist of the 973 Program, Zhejiang Province Distinguished Expert, Chief Physician, Ph.D. Supervisor
• Director, Department of Hematology and Bone Marrow Transplant Center, First Affiliated Hospital of Zhejiang University
• Director, Institute of Hematology, Zhejiang University
• Head, Zhejiang Provincial Engineering Center for Stem Cell and Cellular Immunotherapy
• Member, Expert Panel of the National Key R&D Program on Stem Cell and Translational Research
• Vice Chairman, Expert Committee, China Marrow Donor Program
• Standing Member, Hematology Branch, Chinese Medical Association
• Vice Chairman, Academic Committee, Asian Society of Cellular Therapy
• Executive Committee Member, Asia-Pacific Blood and Marrow Transplantation Society
• Member, International Academic Committee, EBMT
• President, Zhejiang Immunology Society He has conducted extensive research in stem cell basic research and clinical applications of hematopoietic stem cell transplantation, as well as cutting-edge technologies in cellular immunotherapy. He has twice won the National Science and Technology Progress Award (second prize) and led major projects, including the 973 and 863 programs. He has published 278 SCI papers in top journals such as New England Journal of Medicine, Nature, Cell Research, and Lancet Haematology, and holds 21 patents. He has chaired, presented, and delivered keynote speeches at international conferences over 100 times in the past five years and co-edited the first domestic monograph on CAR-T cell immunotherapy, CAR-T Cell Immunotherapy, published by the People’s Medical Publishing House.

Dr. Didier Blaise

• Director, Hematology and Bone Marrow Transplantation Program, Paoli-Calmettes Institute, Aix-Marseille University
• Head of Hematology Department, Aix-Marseille University
• Member, European Society for Medical Oncology (ESMO) and European Hematology Association (EHA)