Biopharmaceutical firm Tolerance Bio, focused on thymus-based immune therapies, announced the publication of preclinical data demonstrating that human induced pluripotent stem cell (iPSC)-derived thymic organoids enabled in-vivo positive selection of human T-cells and reduced tumor burden in a humanised mouse model of melanoma, the company said that the findings were published in Cancer Research Communications.
According to the company, the work used humanised immunodeficient mice implanted with patient-specific iPSC-derived thymic organoids and matched melanoma patient-derived xenografts, enabling the education of human T-cells in a physiologically relevant thymic microenvironment. The tumour growth in mice with thymic organoids was significantly slower and viable tumour content was significantly lower compared to mice lacking the implanted organoids.
The company said the analysis included whole-exome sequencing of tumour cells from mice with thymic organoids, showing elimination of candidate neoantigens and increased intra-tumoral activated T-cells, suggesting enhanced immune surveillance and clearance of tumour cells in the model.
The company claims that these results support the development of its allogeneic, off-the-shelf iPSC thymic cell product and pharmacological thymus-regeneration approaches for aging-related diseases and cancer. The company said it aims to initiate pre-investigational new drug (IND) studies in the near term.
If translated into clinical therapies, the technology could enable enhanced T-cell function and improved outcomes in immune-mediated diseases by restoring thymic education and central immune tolerance, the company said that this could represent a novel avenue in cell therapy and immuno-oncology.
