Editor’s Note:The 54th Annual Scientific Meeting of the International Society for Experimental Hematology (ISEH 2025) was held in Kumamoto, Japan, from September 24–27. The conference brought together leading experts in hematology from around the world to discuss cutting-edge progress in basic hematology, immunology, stem cell research, and cell and gene therapies. During the meeting, Oncology Frontier – Hematology Frontier invited Professor Jianxiang Wang from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Professor Naoki Hosen from Osaka University for a deep dialogue on the latest advances in CAR-T therapy for leukemia. Their discussion covered multiple dimensions — from basic mechanisms and clinical applications to efficacy optimization and future directions — with the shared goal of promoting innovation in CAR-T therapy, advancing international collaboration, and improving global patient access and outcomes. Oncology Frontier – Hematology Frontier: In recent years, CAR-T therapy has achieved breakthrough advances in the treatment of hematologic malignancies. Could you each discuss the major achievements of CAR-T therapy in leukemia and the key challenges that remain?
Prof. Naoki Hosen: CAR-T cell therapy, implemented in Japan for about five years, has become a standard clinical approach, widely used for leukemia, lymphoma, and myeloma patients, significantly improving prognosis. Adverse events like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have markedly decreased, but relapse remains a significant issue. Therefore, I believe CAR-T therapy should be applied at earlier stages.
Prof. Jianxiang Wang: For acute lymphoblastic leukemia (ALL), CD19 CAR-T therapy shows high remission rates in relapsed/refractory patients. However, in acute myeloid leukemia (AML), the lack of ideal targets limits efficacy, and long-term myelosuppression is a concern, with no CAR-T therapies globally approved for AML. Long-term survival is another major challenge, as some ALL patients still rely on allogeneic hematopoietic stem cell transplantation post-CAR-T to reduce relapse risk. Future strategies should focus on enhancing CAR-T efficacy, minimizing transplant dependency, and promoting broader application in acute leukemias.
Oncology Frontier – Hematology Frontier: You led the development and approval of Inaticabtagene Autoleucel, the first domestically developed CD19 CAR-T product in China. Could you share what unique advantages or innovations this therapy offers in terms of mechanism of action?
Prof. Jianxiang Wang: Our CD19 CAR-T utilizes a unique single-chain antibody targeting a distinct epitope on the CD19 antigen, avoiding cross-resistance due to epitope overlap and providing a new option for patients who have failed other CD19 CAR-T therapies. We also adopted an innovative CAR-T structure design, enabling it to function effectively. Clinical trials and real-world data demonstrate excellent safety and efficacy. Pivotal Phase II studies show that grade 3 or higher adverse events and ICANS occur in less than 10% of cases, confirming the therapy’s high efficacy and tolerability. Based on these results, China’s regulatory authority approved Inaticabtagene autoleucel (Inati-cel) for adult ALL patients. Additionally, clinical trials in pediatric patients are underway, with approval for this indication expected soon.
Oncology Frontier – Hematology Frontier: In your talk, you introduced CAR-T and NK cell therapies. Compared with conventional treatments, what unique advantages or potential breakthroughs do these approaches offer in AML?
Prof. Naoki Hosen: As Professor Wang noted, no CAR-T cell therapy for AML has been approved, making such research inherently groundbreaking. Our product has so far only been validated in patients post-allogeneic transplantation, which is a current limitation. This stems from our initial attempts to identify surface antigens specifically expressed on AML cells, which have not been fully successful, leading us to select existing antigens as the first AML target. We are now working to expand the application of this CAR-T therapy to non-transplant patients. Since HLA-DR is not expressed on true human hematopoietic stem cells, we are actively verifying that this CAR-T does not harm normal hematopoietic stem cells. If confirmed, this could broaden the therapy’s application to all AML patients.
Oncology Frontier – Hematology Frontier: Following the pivotal clinical studies, the 2025 EHA Congress further presented real-world data on Inaticabtagene Autoleucel. Based on these findings, how do you evaluate the role of CAR-T therapy in the treatment of ALL and its future prospects?
Prof. Jianxiang Wang: Since its approval and market launch, our CD19 CAR-T therapy has successfully treated over 100 patients in China. Real-world studies demonstrate superior efficacy compared to Phase II clinical trial results, with safety profiles consistent with trial data, further validating its effectiveness and safety in clinical practice. Notably, the therapy excels in minimal residual disease (MRD)-positive patients, effectively eliminating MRD and achieving MRD-negative status, making it a valuable treatment for patients in complete remission with persistent MRD. To address whether this CAR-T therapy can be used as a frontline treatment to reduce chemotherapy cycles or the need for allogeneic transplantation, we have designed and initiated clinical trials for frontline treatment of adult acute lymphoblastic leukemia (ALL). Currently, for both Ph-positive and Ph-negative patients, this CAR-T therapy has demonstrated promising efficacy, significantly clearing minimal residual disease (MRD) and showing potential for long-term survival benefits. Long-term follow-up is ongoing, and we anticipate that the final results will further validate its potential as a frontline treatment, offering a promising option for ALL therapy.
Oncology Frontier – Hematology Frontier: AML presents diverse immune evasion mechanisms. In your opinion, what are the most critical scientific or clinical hurdles that need to be addressed in developing CAR-T and NK cell therapies for AML?
Prof. Naoki Hosen: The primary challenge in AML treatment is the lack of an ideal target antigen specifically expressed on AML cells but not on hematopoietic stem cells. Despite extensive global research, significant breakthroughs remain elusive. Currently, the main strategy to address this is combining CAR-T therapy with allogeneic hematopoietic stem cell transplantation to eliminate leukemia cells, and sometimes normal hematopoietic cells, followed by hematopoietic system reconstitution via transplantation. Thus, the integration of CAR-T and allogeneic transplantation is critical for AML patients. Additionally, a promising alternative is short-term CAR-NK cell therapy. As CAR-NK cells are rapidly cleared by the allogeneic immune system, they can serve as a consolidation therapy for AML, potentially bypassing the need for allogeneic transplantation. This approach may offer an effective treatment option in the future.
Oncology Frontier – Hematology Frontier: Looking ahead, what potential breakthroughs do you foresee in the field of cell therapy? At the same time, how can international collaboration and translational efficiency be further enhanced to accelerate the global application of CAR-T and other cell-based therapies?
Prof. Jianxiang Wang: Currently, CAR-T therapy faces major challenges, including high costs and lengthy preparation cycles, leading to disease progression in some patients during manufacturing. Reducing costs and accelerating production are urgent priorities. Globally, several strategies are being explored. For instance, ‘fast CAR-T’ technology shortens production to one day, with quality control taking about seven days, enabling infusion within seven to ten days. Another cutting-edge approach is in vivo CAR-T, delivering CAR constructs directly into the body via lipid nanoparticles (LNP) or retroviruses, bypassing ex vivo preparation. Preliminary data show feasibility, but long-term efficacy requires validation. Given disparities in CAR-T development and economic conditions across countries, international collaboration is crucial. Multicenter clinical trials can facilitate global technology application, while reasonable pricing ensures accessibility for patients in diverse economies. Additionally, advancing next-generation CAR-T, particularly in vivo approaches, could significantly lower costs and enhance availability, benefiting more patients. However, global immunotherapy development remains uneven, requiring ongoing collaboration and innovation. No mature solutions exist yet, making this a key focus for future research and international cooperation.
Prof. Naoki Hosen: Professor Wang has provided a comprehensive overview, and I would like to discuss from a different perspective. Currently, the greatest challenge for CAR-T therapy is its application to solid tumors. My laboratory is actively exploring this, but significant difficulties persist. AML CAR-T therapy is limited by the lack of specific targets, while developing CAR-T for solid tumors faces more complex issues, including how T cells can effectively infiltrate tumor tissue and overcome immunosuppression from the tumor microenvironment. Overcoming these barriers could enable CAR-T therapy to benefit a broader range of cancer patients.
Expert Profiles
Professor Jianxiang Wang Chief Clinical Expert, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences (CAMS);Director, National Clinical Research Center for Hematologic Diseases;Professor, Chief Physician, Doctoral Supervisor;Among the first tenured professors at Peking Union Medical College, CAMS;National-level selectee of the “National Ten Thousand Talents Program”;Former Chair of the 10th Committee of the Hematology Branch of the Chinese Medical Association;Vice President of the Internal Medicine Physicians Branch of the Chinese Medical Doctor Association, and Vice President of its Hematology Physicians Branch;Recipient of multiple honors including Tianjin Distinguished Expert, Haihe Medical Scholar, Tianjin’s “Top Ten” Healthcare Workers, and “China Good Doctor” monthly award.
Professor Wang has engaged in clinical and basic research on hematologic diseases for many years, possesses extensive experience in diagnosis and treatment, and currently focuses on clinical and translational research in leukemia and hematologic malignancies.
Professor Naoki Hosen Professor, Osaka UniversityResearch Areas: Hematology, Cancer Immunology Research and Career Experience•
Dec 2003 – Mar 2007: Postdoctoral Research Fellow, Stanford University School of Medicine•
May 2007 – Mar 2009: Associate Professor, Graduate School of Medicine, Osaka University• Apr 2009 – Mar 2014: Faculty of Health Sciences, Graduate School of Medicine, Osaka University•
Apr 2014 – Dec 2019: Associate Professor, Faculty of Health Sciences, Graduate School of Medicine, Osaka University• Jan 2020 – Present: Professor, Faculty of Medicine, Graduate School of Medicine, Osaka University•
Nov 2020 – Present: Professor, Immunology Frontier Research Center, Osaka UniversityAwards• 2007: Young Investigator Award, Leukemia Research Fund•
2018: Research Grant, Princess Takamatsu Cancer Research Fund
