Altered Peptide Ligands Impact the Diversity of Polyfunctional Phenotypes in T Cell Receptor Gene-Modified T Cells

摘要: The use of T cell receptor (TCR) gene-modified T cells in adoptive cell transfer has had promising clinical success, but often, simple preclinical evaluation does not necessarily accurately predict treatment efficacy or safety. Preclinical studies generally evaluate one a limited number type 1 cytokines to assess antigen recognition. However, recent have implicated other "typed" effective anti-tumor/viral immunity, and functional evaluations may underestimate cross-reactivity. In this study, we an altered peptide ligand (APL) model multi-dimensional flow cytometry polyfunctionality TCR T cells. Evaluating six the lytic marker CD107a on per basis revealed remarkably diverse polyfunctional phenotypes within single culture among peripheral blood lymphocyte (PBL) donors. This assessment identified unexpected phenotypes, including cells producing both 2 cytokines, highlighted interferon γneg (IFNγneg) antigen-reactive populations overlooked our previous studies. Additionally, APLs skewed be less polyfunctional, which was related changes TCR-peptide-major histocompatibility complex (pMHC) affinity. A better understanding diversity help identify optimal therapeutic responses, anticipate off-target recognition, improve design delivery