PHILADELPHIA, PA — Tolerance Bio announced the publication of new research showing that lab-grown human thymic organoids can restore immune function and suppress tumor growth in melanoma, marking a potential breakthrough in personalized cancer treatment and immune system regeneration.
The peer-reviewed study, titled “Patient-specific autologous thymic organoids support functional T-cell education leading to antitumor activity in humanized mice with melanoma xenografts,” was published in Cancer Research Communications, a journal of the American Association for Cancer Research. The work was led by Antonio Jimeno, M.D., Ph.D., of the University of Colorado Anschutz School of Medicine, and Holger A. Russ, Ph.D., of the University of Florida and scientific co-founder of Tolerance Bio.
Researchers implanted thymic cells derived from induced pluripotent stem cells (iPSCs) into immune-deficient humanized mice alongside matching tumor tissue from a melanoma patient. The tumors in mice bearing thymic organoids grew significantly slower and showed reduced viable melanoma content compared to control groups, with increased activated T cells and evidence of enhanced 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,” said Dr. Jimeno. “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.”
“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,” said 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 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.”
The findings establish proof of principle for Tolerance Bio’s approach to thymic regeneration and suggest broad potential for treating cancer and age-related immune dysfunction.
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