Neoantigen-specific TCR expansion in stimulated T-cell cultures.

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Neoantigen-specific TCR expansion in stimulated T-cell cultures. Neoantigen-specific TCR expansion in stimulated T-cell cultures. Peptides generated from the eliminated mutation-associated neoantigen candidates were synthesized and used to pulse autologous peripheral T cells for patient CGLU116. T cells were stimulated with respective mutant and wild-type peptides and cultured for 10 days, followed by next-generation TCR sequencing of expanded T-cell cultures. Reactive TCR clonotypes were matched to clones found in infiltrating tumor lymphocytes. Neoantigen-specific TCR reactivity was observed for the mutant peptides associated with mutant HELB987P>S (SASPLSVV; A), SLC26A7117R>Q (ISANAVEQIV; B), and PGAP1903Y>F (AFGSAHLFR and VIAFGSAHLFR; C) compared with their wild-type counterparts. An oligoclonal TCR expansion was observed for both mutant (STPSASPLSV) and wild-type (STPSASPLPVV) peptides associated with a single-base substitution in HELB (D). Adjusted P values are given for pairwise comparisons between productive frequencies in peptide-stimulated versus unstimulated T cells. Solid bars represent mutant peptides, and bars with diagonal pattern denote wild-type peptides. Valsamo Anagnostou et al. Cancer Discov 2017;7:264-276 ©2017 by American Association for Cancer Research