Figure 2.

Superiority of healthy donor-derived peripheral blood mononuclear cells (PBMCs) over patient-derived tumor infiltrating lymphocytes (TILs)/PBMCs as a source of therapeutically valuable TCRs. Cancer patients are a limited source for tumor-specific TCR identification, as relevant tumor tissue is not always accessible for TIL isolation and peripheral blood may have low lymphocyte count due to extensive cancer treatment. In addition, the TCR repertoire is often skewed towards lower avidity due to tumor pressure. This results in a reduced probability of finding highly functional neoantigen-specific TCRs, thus limiting access to TRC-based therapies. On the contrary, healthy donor-derived PBMCs are not only an easily accessible source but also offer a broader repertoire to interrogate in respect of any potential specificity, including tumor neoantigens. Higher number of patients would be then eligible for personalized ACT.