Recurrent Immunogenic Neoantigens and Their Cognate T-cell Receptors in Treatment-Resistant Metastatic Prostate Cancer.

ABSTRACT: New approaches that generate long-lasting therapeutic responses in patients with therapy-resistant metastatic cancer are urgently needed. To address this challenge, we developed Spot Neoantigens in Metastases (SpotNeoMet), a novel data-driven pipeline that systematically identifies recurrently presented neopeptides in treatment-resistant patients. We identified seven therapy resistance mutations predicted to produce neopeptides presented by common HLAs. Using HLA immunopeptidomics, we discovered three novel neopeptides derived from androgen receptor (AR) H875Y, a common metastatic castration-resistant prostate cancer (mCRPC) mutation. We validated these neoantigens as highly immunogenic and then isolated and characterized cognate T-cell receptors (TCR) from healthy donor peripheral blood m

SUBMITTER: Gumpert N 

PROVIDER: S-EPMC12749549 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature