Editor's Note: To further enhance the diagnosis and treatment of leukemia and lymphoma in China, the 8th Hematology Academic Conference, jointly organized by the Chinese Society of Clinical Oncology (CSCO), CSCO Leukemia Expert Committee, and Lymphoma Expert Committee, and co-hosted by Harbin Institute of Hematology and Oncology and Peking University Cancer Hospital, was held grandly in Harbin from July 26 to 28. The conference aimed to provide an important platform for in-depth learning and extensive exchange among experts and scholars in the field of hematological tumors. On this occasion, "Oncology Frontier - Hematology Frontier" specially invited Dr. He Huang from The First Affiliated Hospital , Zhejiang University School of Medicine to discuss the frontier topic of cellular immunotherapy.

Oncology Frontier – Hematology Frontier: With the development of cellular immunotherapy technology, new cellular immunotherapies have shown great potential in treating hematological and solid tumors. Compared with traditional cellular immunotherapies, what innovations do new cellular immunotherapies have? How do these innovations improve treatment efficacy?

Dr. He Huang: At this 8th CSCO Hematology Academic Conference, cellular immunotherapy was established as one of the core topics, highlighting its significance in the medical field. This topic not only underscores the forefront position of cellular immunotherapy but also emphasizes its critical role in treating hematological tumors, showcasing its vast potential in future medical development. Through over ten years of in-depth exploration and practice, cellular immunotherapy has become indispensable in treating hematological malignancies, thanks to the meticulous engineering modifications of immune cells. To date, 11 cellular immunotherapy drugs have been successfully launched globally, including 5 in China targeting CD19 and B cell maturation antigen (BCMA). These drugs are widely used in treating relapsed/refractory lymphoma, multiple myeloma, and leukemia, and their excellent clinical efficacy and immense potential have been validated.

In exploring new cellular immunotherapies, we strive for dual leaps in efficacy and safety based on existing drugs. The Bone Marrow Transplant Center at the First Affiliated Hospital of Zhejiang University School of Medicine has made significant progress in this regard, particularly in researching new targets for treating hematological malignancies. For example, CAR-T cell therapy targeting CD7 has brought hope to patients with T-cell acute lymphoblastic leukemia (ALL), T-cell lymphoblastic lymphoma, and some acute myeloid leukemia (AML) patients expressing CD7. Our team’s research on CD7 CAR-T cell therapy has been published in the “New England Journal of Medicine” this year. This study further reveals that combining CD7 CAR-T cell therapy with haploidentical hematopoietic stem cell transplantation (HID-HSCT) using a sequential “integrated” treatment strategy can safely and effectively alleviate the disease.

Additionally, enhancing the efficacy of existing cellular immunotherapy drugs to achieve higher remission rates and lower recurrence rates is the core of innovative research. We can utilize advanced technologies such as synthetic biology and gene editing to precisely modify drug action pathways, significantly improving their therapeutic effects. In this regard, domestic researchers have made numerous innovative attempts, demonstrating extraordinary creativity and execution, jointly driving the vigorous development of innovative drug research and development in China. Looking ahead, we will continue to uphold the spirit of innovation, promote the widespread application of new cellular immunotherapy drugs in clinical practice, and contribute more to the medical field in China and globally.

Oncology Frontier – Hematology Frontier: The translational process of new cellular immunotherapies from the laboratory to the clinic is full of challenges. Could you share the main challenges currently faced and the strategies your team has adopted to promote clinical translation?

Dr. He Huang: New cellular immunotherapy aims to address current challenges and key scientific issues in the field of cell therapy, achieving breakthroughs in disease treatment through basic research-driven clinical translation. The primary task is to refine clinical problems into scientific questions. The main challenges in the clinical field are significantly improving treatment efficacy and effectively reducing complications. The ultimate goal is to explore curative treatment options, but the path to achieving this goal is fraught with obstacles and challenges, requiring our continuous efforts and overcoming difficulties.

Another critical step is obtaining clinical certification after designing drugs that meet clinical needs, including dual confirmation of safety and efficacy. Usually, drugs must undergo rigorous clinical research phases, followed by submitting detailed application materials to the National Medical Products Administration, undergoing multiple reviews until successfully marketed. This process is not only lengthy and complex but also demands enormous resources. For Chinese enterprises, this is undoubtedly a daunting challenge, requiring overcoming numerous difficulties and investing substantial human, material, and financial resources. However, we should always maintain an optimistic spirit. Through close cooperation between Chinese doctors and local innovative enterprises, China’s cellular immunotherapy technology is expected to reach new heights.

Oncology Frontier – Hematology Frontier: The indications and patient selection for new cellular immunotherapies are critical issues in clinical application. Could you introduce the main types of tumors and patient groups currently suitable for new cellular immunotherapies? What research directions do you think are worth focusing on in the future in the field of new cellular immunotherapy?

Dr. He Huang: To date, approved cellular immunotherapy drugs mainly focus on B-lineage hematological tumors, covering leukemia and lymphoma, targeting specific cell surface markers such as BCMA and CD19. These drugs enhance the immune system’s ability to recognize and eliminate tumor cells through specific binding to these markers. However, it is essential to note that there are many types of malignant hematological diseases, including myeloid leukemia and T-lineage hematological tumors. In China, many drugs targeting T-lineage hematological tumors have entered clinical research stages or obtained clinical trial licenses (IND), mainly targeting CD7 or CD5. For myeloid hematological tumors, new targets such as CD123 and CD38 have shown potential application value, with relevant drug research actively advancing. Some drugs have already entered clinical research stages, showing promising prospects.

During drug development, safety and efficacy are key factors in evaluating whether a drug can enter clinical application. When new drugs demonstrate good safety and efficacy in preclinical studies, they are likely to enter the clinical research stage approved by the National Medical Products Administration. Many drugs in the IND stage in China are actively seeking approval to enter clinical trials. This accelerates the drug development process and provides patients with more treatment options, improving treatment outcomes and quality of life. With the continuous advancement of medical research and technology, we expect to see more innovative and effective treatment methods widely applied in hematological tumor treatment. These new treatment methods bring new hope to patients and significantly promote the development of the entire hematological tumor treatment field.

Dr. He Huang

• Qiushi Distinguished Professor, Zhejiang University, Chief Scientist of 973 Program
• Chief Physician and Doctoral Supervisor, Zhejiang Provincial Special Expert
• Director, Institute of Hematology, Zhejiang University
• Director, Zhejiang Provincial Engineering Research Center for Stem Cell and Cellular Immunotherapy
• Chief Scientist, “Hematology and Immune Diseases” at Liangzhu Laboratory
• Director, Bone Marrow Transplant Center, First Affiliated Hospital of Zhejiang University School of Medicine
• Member, Expert Group of “Stem Cell and Translational Research” Key Project, National Key R&D Program
• Member, Third National Medical Professional Degree Graduate Education Steering Committee
• Vice Chairman, Asia Cellular Therapy Organization
• Executive Committee Member, International Academic Committee of Asia-Pacific International Bone Marrow Transplant Organization
• Member, International Academic Committee of European Bone Marrow Transplant Organization
• Deputy Director, Expert Committee of China Marrow Donor Program
• Standing Committee Member, Hematology Branch of Chinese Medical Association