On October 27, 2025 Tolerance Bio, a biopharmaceutical company pioneering innovative approaches to extending healthspan by preserving, restoring, and manipulating the function of the thymus, the master regulator of immune tolerance, reported the publication of a scientific article titled "Patient-specific autologous thymic organoids support functional T-cell education leading to antitumor activity in humanized mice with melanoma xenografts" in Cancer Research Communications, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). The research was led by Antonio Jimeno, M.D., Ph.D., from the Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz School of Medicine, and Holger A. Russ, Ph.D., from the Diabetes Institute and the Department of Pharmacology and Therapeutics, College of Medicine at the University of Florida, Gainesville, and scientific co-founder of Tolerance Bio.

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The contributing teams utilized a novel approach, implanting patient-derived thymic cells generated via direct differentiation of induced pluripotent stem cells (iPSCs) into thymectomized and humanized immune-deficient mice, along with matched tumor tissues from a patient with metastatic melanoma. The key finding was that tumors implanted in mice with human thymic tissue grew significantly slower compared to tumors implanted in control and in humanized mice without thymic tissue. Viable melanoma content was also significantly decreased in mice bearing thymic organoids, associated with an increase in intra-tumoral activated T-cells. Whole gene sequencing identified multiple candidate neoantigens that were eliminated in cancer cells in thymus-bearing mice, suggesting a more effective identification and T-cell-driven tumor clearance.

"An experiment is only as good as the models used to conduct it. Over the last 15 years, we have generated increasingly complex laboratory and mouse models that can bear both human immune and cancer cells, which we call humanized mice, to realize the promise of immune therapy. A fundamental limitation of humanized mice, generated with donor blood stem cells and implanted with mismatched patient tumors, is that the fidelity of the interaction between the immune and tumor cells is limited by lack of the organ that facilitates immune cell education, the thymus," said Dr. Jimeno.

"Here we report the successful generation of a novel model that incorporates functional thymic organoids derived from iPSC generated using patient peripheral blood with tumors from the same patient, providing an important step towards improved personalized models," remarked Dr. Russ.

"These results represent meaningful advance in oncology, both from a therapeutic and a diagnostic point of view, as iPSC thymic cells have the potential to serve as a cell therapy for cancer, alone or along immune agents, the patient derived xenograft model can improve new drug development by more accurately identifying promising drugs and vaccines, and it will allow for personalized medicine by testing which immune therapy is more likely to work for a specific patient," added Dr. Jimeno. "We have a lot of work ahead, but I am looking forward to extending our interdisciplinary work into the future to realize this potential."

"Tolerance Bio is proud to collaborate with Dr. Jimeno and Dr. Russ, and their superb teams at U. Colorado and U. Florida. Their work lays the foundation for the use of iPSC thymic cells in immune diseases, including cancer," said Dr. Francisco Leon, M.D., Ph. D., CEO of Tolerance Bio. "The changes in the tumor growth kinetics provide critical proof of principle for the ability of iPSC thymic cells to reconstitute a T cell immune system in vivo with beneficial functional consequences. As we advance towards the clinic, we have developed a robust manufacturing process for our allogenic, off-the-shelf iPSC thymic cell product, and we plan to initiate pre-investigational new drug (IND) studies in the near future."

(Press release, Tolerance Bio, OCT 27, 2025, View Source [SID1234657047])