Antigen Experienced T Cells from Peripheral Blood Recognize p53 Neoantigens.

Purpose: The purpose of this study was to evaluate antigen experienced T cells in peripheral blood lymphocytes (PBL) for responses to p53 neoantigens.

Experimental Design: PBLs from patients with a mutated tumor were sorted for antigen-experienced T cells and stimulation (IVS) was performed with p53 neoantigens. The IVS cultures were stimulated with antigen-presenting cells expressing p53 neoantigens, enriched for 41BB/OX40 and grown with rapid expansion protocol.

Results: T-cell responses were not observed in the PBLs of 4 patients who did not have tumor-infiltrating lymphocyte (TIL) responses to mutated . In contrast, 5 patients with TIL responses to mutated also had similar T-cell responses in their PBLs, indicating that the PBLs and TILs were congruent in p53 neoantigen reactivity. CD4 and CD8 T cells were specific for p53, p53, or p53 neoantigens, including a 78% reactive T-cell culture against p53 and HLA-A*02:01. Tracking clonotypes (clonality, top ranked, and mutation-specific) supported the enrichment of p53 neoantigen-reactive T cells from PBLs. The same T-cell receptor (TCR) from the TIL was found in the IVS cultures in three cases and multiple unique TCRs were found in another patient. mutation-specific T cells also recognized tumor cell lines bearing the appropriate human leukocyte antigen restriction element and mutation, indicating these T cells could recognize processed and presented p53 neoantigens.

Conclusions: PBL was a noninvasive source of T cells targeting mutations for cell therapy and can provide a window into intratumoral p53 neoantigen immune responses..