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Immunologic Recognition of a Shared p53 Mutated Neoantigen in a Patient with Metastatic Colorectal Cancer.

Cancer Immunol Res. 2019-04; 
LoWinifred,ParkhurstMaria,RobbinsPaul F,TranEric,LuYong-Chen,JiaLi,GartnerJared J,PasettoAnna,DenigerDrew,MalekzadehParisa,SheltonThomas E,PrickettTodd,RaySatyajit,KivitzScott,PariaBiman C,KrileyIsaac,SchrumpDavid S,RosenbergStev
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摘要

Adoptive cell therapy (ACT) with T cells targeting neoantigens can mediate durable responses in patients with metastatic cancer. Cell therapies targeting common shared antigens for epithelial cancers are not yet broadly available. Here, we report the identification and characterization in one patient of T-cell receptors (TCRs) recognizing mutated p53 p.R175H, which is shared among a subset of patients with cancer. Tumor-infiltrating lymphocytes were screened for recognition of mutated neoantigens in a patient with metastatic colorectal cancer. HLA-A*0201-restricted recognition of mutated p53 p.R175H was identified, and the minimal peptide epitope was HMTEVVRC. Reactive T cells were isolated by tetramer so... More

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