From November 14th to 17th, 2024, the Cellular Therapy and Immunotherapy Conference (CTI) was grandly held in Hangzhou, China, gathering top experts, scholars, and industry leaders in the field of global cell therapy and immune therapy. The conference served not only as an international platform for academic exchange but also as an important window to showcase the latest scientific research and promote the development of the field. "Hematology Frontier" specially invited the conference chair and the chairman of the Asian Cellular Therapy Organization (ACTO), Dr. Akihiro Shimosaka, to share his profound insights on immune cell therapy, regenerative medicine, gene therapy, and the application of exosomes.

Hematology Frontier：What’s your current focus in research in the fields of cell therapy and immunotherapy?

Dr. Akihiro Shimosaka：In the field of cellular therapy and immunotherapy, my research focuses on a variety of therapeutic strategies and technical approaches. I am committed to developing a range of cell therapies, including immune cell therapies and applications in regenerative medicine, as well as exosomes. The common goal of these treatment methods is to use cellular and molecular mechanisms to treat hematological malignancies and improve patients’ quality of life.

Furthermore, I have nearly 50 years of experience in drug development, drug submission, and drug regulation, and have established long-term and in-depth cooperation and exchange with multiple global large pharmaceutical companies and drug regulatory authorities in various countries. This cooperation is crucial to ensuring that our research findings can be safely and effectively translated into clinical applications. Through communication and collaboration with regulatory authorities, we can ensure that the development of new technologies follows strict scientific standards and ethical norms.

Specifically, I focus on the following areas:

Regenerative Medicine: Aiming to restore the function of damaged tissues by stimulating or replacing them. This involves stem cell technology, especially the application of induced pluripotent stem cells (iPS cells), which have the ability to differentiate into various cell types.

Immunotherapy: Primarily using the patient’s immune system to combat malignant tumors, including genetically engineering T cells to recognize and attack cancer cells.

Gene Therapy: Aiming to use healthy genes to fill in or replace missing or diseased genes to treat genetic diseases such as cystic fibrosis, sickle cell disease, and sickle cell anemia.

Exosomes: These are small vesicles secreted by cells, carrying proteins, RNA, and other molecules that can affect the function of other cells. Their ability to cross cell membranes and not easily trigger immune responses gives them a unique advantage in the in vivo delivery of drugs such as genes and anti-tumor agents, making them highly application potential. Dr. Klatz, President of the American Academy of Anti-Aging Medicine, said, “Exosomes are the next direction for stem cell technology development.”

Hematology Frontier：Can you share something you consider to be the most innovative in cellular or immunotherapy and tell why it impresses you?

Dr. Akihiro Shimosaka：In the field of cell or immunotherapy, I believe the two most innovative directions are the application of exosomes in immune cell therapy and the role of CD133+/CD34+ peripheral blood stem cells in regenerative medicine.

Firstly, the application of exosomes in immune cell therapy is a very cutting-edge and emerging field. Exosomes are microvesicles secreted by dendritic cells (DCs), carrying a variety of genetic materials that can affect the function of recipient cells. In immunotherapy, exosomes can serve as a platform for antigen presentation, activating immune responses, and can also carry molecules that suppress immune responses, making exosomes play a role in both immune activation and immune suppression. Exosomes must carry necessary information, such as antigens or signals, to function effectively, which is a key characteristic of their use as therapeutic tools.

Professor Herbert Kim Lyerly, former director of the Cancer Center at Duke University, is one of the earliest scholars in the world to conduct exosome research, with over 20 years of experience in DC tumor vaccine research, accumulating a wealth of research experience and data on tumor neoantigens and exosomes. At this conference, Professor Lyerly presented a lecture titled “Exosomes and mRNA as Novel Cancer Therapies,” and the research data confirmed the effectiveness of exosomes in immunotherapy, which I am very much looking forward to. I will collaborate with Professor Lyerly to jointly develop a universal DC+ exosome tumor vaccine and conduct clinical trials and drug submissions in the United States, Japan, and China, so please stay tuned.

Secondly, the application of CD133+/CD34+ peripheral blood stem cells in regenerative medicine is also an innovative direction. In Japan, CD133+/CD34+ peripheral blood stem cells are used to promote the regeneration of new blood vessels, which is crucial for the protection of diabetic patients’ legs and to avoid amputation, and this advanced new therapy has been approved by regulatory authorities. The successful application of this therapy demonstrates the great potential of regenerative therapy in clinical practice and emphasizes the importance of a therapy approval system in addition to the drug approval system.

The development of these two fields not only demonstrates the innovation of cell and immunotherapy but also provides new treatment options for patients, bringing clinical benefits. As research deepens, we can expect to see the application of these therapies in the treatment of a broader range of diseases.

Hematology Frontier：What special insights or experiences do you gain from participating in this international conference on cellular or immunotherapy?

Dr. Akihiro Shimosaka：I have come to deeply appreciate the importance of combining the latest cutting-edge advancements with existing technological methods. The conference covered a multitude of technologies, and it is essential for us to integrate various techniques to meet the complex and changing therapeutic needs, devising more comprehensive treatment plans to more effectively address the challenges of various diseases. Additionally, this conference served as a valuable platform for sharing information. We were fortunate to engage in dialogue with industry leaders and representatives from regulatory agencies; such multi-party engagement is crucial for propelling the development of cell and immunotherapies.

Hematology Frontier：As we are looking to the future, what’s your expectation or wishes for the future of cellular or immunotherapy?

Dr. Akihiro Shimosaka：First and foremost, I anticipate that these therapies will become more precise and personalized. Current treatment models often resemble drug distribution, where one drug is applied to all patients. However, future cell or immunotherapies should shift towards personalized treatments tailored to the specific conditions of each patient. This means that treatment plans will be designed based on the patient’s genetic information, tumor characteristics, and immune status to achieve the best therapeutic effects and minimize side effects.

Secondly, to achieve this level of personalized treatment, we need the support of corresponding regulations and policies. This includes the establishment and improvement of a regulatory framework for cell therapies to ensure that patients can receive safer, more effective, and more individualized innovative treatments.

Lastly, we also look forward to the future integration of cell therapies into public medical insurance systems, further enhancing the accessibility and equity of treatments and ensuring that patients can widely benefit from these innovative research outcomes.

In summary, I am filled with anticipation for the future of cell and immunotherapies, hoping they will become more precise and personalized treatment options, supported by policies and insurance systems, thus benefiting every patient.

Since the 1990s, I have been working closely with Chinese doctors. My research outcomes have facilitated the application of hematopoietic regulatory factors represented by granulocyte colony-stimulating factor in clinical practice. This has led to the gradual replacement of bone marrow hematopoietic stem cell transplantation with peripheral blood hematopoietic stem cell transplantation since the 1990s and has promoted the global development of hematopoietic stem cell transplantation technology, benefiting many Chinese patients.

Building on this foundation, the half-identical transplantation technology independently developed by the Hematology Institute of Peking University People’s Hospital has achieved significant results in the treatment of children with acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). The importance of this technology lies in its ability to perform transplantations without the need for a fully matched human leukocyte antigen (HLA) donor from siblings, solving the problem that many patients in the past could not receive treatment due to the lack of a matching donor. I am very pleased to collaborate with them in advancing this significant medical development.