The work supports pursuing allogeneic iPSC-derived thymic cells and pharmacological thymus-regeneration strategies for aging-related diseases and cancer, with pre-IND steps anticipated soon.

Tolerance Bio has demonstrated that patient-specific, iPSC-derived thymic organoids can educate T-cells in a physiological thymic environment, leading to reduced melanoma growth in a humanized mouse model.

In the study, human thymic cells generated from induced pluripotent stem cells were implanted into thymectomized, humanized mice alongside patient-derived melanoma tissues, showing slower tumor growth and lower viable tumor content versus controls.

The experiments used a humanized immunodeficient mouse model with patient-specific iPSC-derived thymic organoids and matched melanoma xenografts to educate T-cells, resulting in improved tumor control compared with organoid-free controls.

Clinically, this technology could enhance T-cell function and outcomes in immune-related diseases by restoring thymic education and central immune tolerance, offering a potential new avenue in cell therapy and immuno-oncology.

Tolerance Bio aims to develop off-the-shelf allogeneic thymic cell products for immune diseases, including cancer, and plans to begin pre-IND studies to advance clinical applications.

Leading the research were Dr. Antonio Jimeno (University of Colorado) and Dr. Holger Russ (University of Florida), whose work highlights the potential of iPSC-derived thymic cells for cancer immunotherapy and personalized medicine.

The model overcomes a limitation of traditional humanized mice by incorporating functional thymic tissue, enhancing the fidelity of immune-tumor interactions and enabling a more personalized platform for testing therapies.

Whole-exome sequencing of tumors from mice with thymic organoids showed elimination of several neoantigens and an increase in intra-tumoral activated T-cells, signaling stronger immune surveillance and tumor clearance.

Overall, tumors in the thymic organoid cohort exhibited higher intra-tumoral activated T-cells and loss of multiple neoantigens, indicating an enhanced anti-tumor immune response.