Organ Transplants Without Immunosuppressants: A Revolutionary New Immunotherapy Technology
The Center for Immunotherapeutics and Disease, established in 2021, focuses on developing cutting-edge immunotherapies that bridge basic science and clinical applications. It is currently conducting a multi-center, investigator-initiated clinical trial exploring organ transplantation without immunosuppressive drugs. We spoke with Vice-Director Koichiro Uchida about the center’s immunotherapy research, which is drawing worldwide interest.
Organ transplantation is the definitive treatment for organ failure that cannot be addressed by conventional therapies. However, transplanted organs are often rejected by the recipient’s immune system. To prevent this, patients often must take multiple immunosuppressive medications for the rest of their lives.
While immunosuppressants are essential, systematically suppressing the immune system increases a patient’s vulnerability to infections, including viral diseases. Long-term use can also impair the body’s ability to control cancer cell growth. Additionally, immunosuppressants can cause nephrotoxicity, further complicating patient care. As a result, transplant recipients often have to live with major lifestyle limitations following surgery.
The Center for Immunotherapeutics and Disease aims to mitigate these risks and improve the quality of life for transplant patients by developing cell-based therapies that selectively suppress immune responses against transplanted organs.
Our research team has developed “inducible suppressor T cells (JB-101)” to artificially induce immunotolerance, a state where the immune system accepts a transplant. In a 2016 clinical study at Hokkaido University, JB-101 enabled 7 out of 10 liver transplant patients to fully discontinue immunosuppressive therapy.
In 2019, the team collaborated with JUNTEN BIO Co., Ltd., a drug discovery venture originating from Juntendo University, to develop a stable production process for JB-101 and began full-scale efforts toward its clinical application.
While new drugs and therapies typically undergo a multi-year approval process, JB-101 was designated a “Pioneering Drug” by Japan’s Ministry of Health, Labour and Welfare in 2020. This designation fast-tracks the drug’s approval process, recognizing its innovative nature, the severity of the condition it addresses, its exceptional potential, and Japan’s goal of being the first country to develop this treatment.
A subsequent multi-center, investigator-initiated clinical trial was launched in 2021 at five leading Japanese liver transplant institutions, enrolling 10 liver transplant patients.
In the clinical trial, immune cells from the patient and donor are cultured with antibodies that induce immune tolerance. The resulting JB-101 is administered following the liver transplant, and immunosuppressive medication is gradually reduced and eventually discontinued to assess both efficacy and safety. The goal is to commercialize JB-101 as a regenerative medical product, as defined by the Japanese government, by fiscal year 2026.
The Center for Immunotherapeutics and Disease stands out due to the close collaboration with clinicians and researchers with diverse areas of expertise. Its approach to “reverse translational research” incorporates insights from clinical practice back into basic research, creating a cycle where discoveries from basic science are effectively translated back into clinical applications.
While the Center is advancing clinical trials for practical use in medical settings, it also investigates the mechanisms underlying immunotolerance and rejection. The team uses model mice to validate findings from clinical specimens and investigates, at the molecular level, why treatments work for some patients but not others Clarifying the mechanisms of immunotolerance could extend applications to autoimmune and allergic diseases, in which the immune system attacks the body’s own tissues. The Center has also begun exploring approaches targeting disease-specific genes in collaboration with the Department of Internal Medicine and Rheumatology.
Making immunotherapy accessible to a wider range of patients requires a collaborative effort from professionals across multiple disciplines. At the Center, this project is driven by a team of experts from various fields. This includes the Manufacturing and Quality Control Group, which oversees production and quality assurance; the Clinical Trial and Clinical Research Group, which develops research protocols and coordinates with regulatory authorities; and the Clinical Trial Coordination Office.
In addition to producing JB-101 at Juntendo University’s Cell Processing Center (CPC), the Center has established a robust research and development framework through industry–government–academia collaboration, engaging multiple medical departments within the university as well as partner institutions participating in the clinical trials.
The Center is pursuing international expansion, particularly in regions with a high number of organ transplants, such as the United States, where kidney transplant cases are more frequent than in Japan. We are currently conducting a Phase I kidney transplant trial in collaboration with the University of California, Davis, and are advancing the transfer of our immune cell therapy technology. We are also working to share our medical technologies globally, adapting them to different healthcare systems, and developing new formulations that meet global standards.
While current clinical trials are focused on liver transplants, we are exploring JB-101 for living donor kidney transplants, for late-stage liver transplant patients several years post-transplant, as well as in brain-dead donor transplants, which are expected to become more common in the future.
There is still room to improve JB-101. Currently, treatment requires collecting T cells from both the patient and donor via apheresis, an extracorporeal circulation technique similar to dialysis, to isolate the necessary components. This process is time-consuming and places a significant burden on both parties, highlighting the need for a method that is equally effective but less burdensome. Building on its extensive experience, the Center aims to develop faster, more efficient immune cell therapies and immune monitoring techniques.
To raise awareness of its immunotolerance project, the Center for Immunotherapeutics and Disease shares information through its website, open lectures, academic conferences, and other channels. A few years ago, a junior high school student reached out after learning about JB-101 and expressing interest in the treatment. The boy, who lives with an incurable condition that might one day require a living donor liver transplant, was researching the topic for a school project. We invited him to the Center, where specialists from each field involved in the project explained their work. He later shared that this experience deepened his understanding of the research and strengthened his interest in transplant medicine.
Opportunities like this are extremely valuable to us. Unmet medical needs—such as the challenges posed by immunosuppressants in organ transplantation and autoimmune diseases for which effective treatments have yet to be established—can be difficult to fully recognize, even by medical professionals who work closely with patients every day. Because this project involves collaboration among a wide range of experts, including basic researchers, regulatory specialists, and pharmaceutical companies, it is essential to listen to patients’ perspectives.
What we do is guided by the principle of “science for patients, not science for its own sake.” Guided by this philosophy, we conduct basic research, clinical research, and clinical trials. We will continue tackling challenging problems that remain unresolved in current medical practice, applying immunological knowledge and methods to clinical specimens, and initiating new clinical research projects to translate our findings into practical medical applications.
Vice Director, Center for Immunotherapeutics and Disease, Advanced Research Institute for Health Science, Juntendo University
Dr. Uchida graduated from Juntendo University Faculty of Medicine in 2004 and earned his Ph.D. in 2012. After working in the First Department of Surgery at Hokkaido University Hospital, he became Vice-Director of the Center for Immunotherapeutics and Disease, Advanced Research Institute for Health Science at Juntendo University. He also serves as Associate Professor in the Department of Surgery, Division of Digestive Surgery (Hepato-Biliary-Pancreatic Surgery) at Juntendo University Graduate School of Medicine, and as Associate Professor in the Department of Hepato-Biliary-Pancreatic Surgery at the Graduate School of Medicine. He was involved in establishing JUNTEN BIO Inc., a university-based drug discovery venture. His research focuses on post-transplant immunotolerance, immune monitoring, and transplant organ preservation.
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