利用自体结直肠肿瘤类器官提高从循环淋巴细胞中鉴定肿瘤特异性 TCR 的效率

The identification of effective T cell receptors (TCRs) with specific reactivity against tumor cells is critical for the efficacy of TCR-engineered T cell therapy.

However, different approaches for screening effective TCRs remain to be explored.

We developed an optimized approach to identify effective TCRs based on an organoid culture system with patient-derived tumor cells in the presence of oxaliplatin and autologous dendritic cells. By coculturing the immunogenic debris of patient tumor cells from the organoid, we successfully enriched tumor-reactive CD4 + and CD8 + T cells, enhanced the activation and proliferation of T cells, and could facilitate the identification of tumor-reactive CD8 + T cells from patients with MHC I-downregulated tumors.

We further used autologous tumor organoids to verify that candidate tumor-specific TCRs can elicit patient-specific tumor recognition and killing when expressed in allogeneic T cells.

Our organoid-based tumor-reactive T cell enrichment system and TCR screening validation platform provide an empirical strategy for the isolation of tumor-reactive T cells and can advance the study of TCR-engineered T cell therapy.