Neoantigen-specific CD4+tumor-infiltrating lymphocytes are potent effectors identified within adoptive cell therapy products for metastatic melanoma patients

• DOI: 10.1136/jitc-2023-007288
• Publication Date: 2024-02-09T16:38:21Z
• Authors: MacLean S. Hall; Jamie K. Teer; Xiaoqing Yu; Holly Branthoover; Sebastian Snedal; Madeline Rodrigue...; Luz Nagle; Ellen Scott; Ben Schachner; Patrick Innamarato; Amy M. Hall; Jamie Blauvelt; Carolyn J. Rich; Allison D. Richards; Jake Ceccarelli; TJ Langer; Sean J. Yoder; Matthew S. Beatty; Cheryl A. Cox; Jane L. Messina; Daniel Abate-Daga; James J. Mule; John E. Mullinax; Amod A. Sarnaik; Shari Pilon-Thomas
• Keywords: Tumor-infiltrating lymphocytes; Adoptive Cell Transfer

Background Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is a promising immunotherapeutic approach for patients advanced solid tumors. While numerous advances have been made, the contribution of neoantigen-specific CD4 + T cells within TIL infusion products remains underexplored and therefore offers significant opportunity progress. Methods We analyzed infused from metastatic melanoma previously treated ACT presence cells. TILs were enriched on reactivity to neoantigen peptides derived prioritized patient sample-directed mutanome analysis. Enriched further investigated establish clonal response respect function, transcriptomics, persistence following ACT. Results discovered that clones predominantly present in both therapeutic responders non-responders. demonstrated an effector cytotoxicity toward autologous tumor major histocompatibility complex class II-dependent manner. These results validated by paired TCR single RNA sequencing, which elucidated transcriptomic profiles distinct TIL. Conclusions Despite methods often focus CD8+T cells, our study supports importance prospective identification as they are potent source tumor-specific effectors. advocate inclusion future protocols strategy improve antitumor immunity.