A T cell receptor specific for an HLA-A*03:01-restricted epitope in the endogenous retrovirus ERV-K-Env exhibits limited recognition of its cognate epitope

AT细胞受体特异性识别内源性逆转录病毒ERV-K-Env中HLA-A*03:01限制性表位,但对其同源表位的识别能力有限。

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作者:Erin E Grundy ,Lauren C Shaw ,Loretta Wang ,Abigail V Lee ,James Castro Argueta ,Daniel J Powell Jr ,Mario Ostrowski ,R Brad Jones ,C Russell Y Cruz ,Heather Gordish-Dressman ,Nicole P Chappell ,Catherine M Bollard ,Katherine B Chiappinelli

Abstract

Transposable elements (TEs) are often expressed at higher levels in tumor cells than normal cells, implicating these genomic regions as an untapped pool of tumor-associated antigens. In ovarian cancer (OC), protein from the TE ERV-K is frequently expressed by tumor cells. Here we determined whether the targeting of previously identified epitope in the envelope gene (env) of ERV-K resulted in target antigen specificity against cancer cells. We found that transducing healthy donor T cells with an ERV-K-Env-specific T cell receptor construct resulted in antigen specificity only when co-cultured with HLA-A*03:01 B lymphoblastoid cells. Furthermore, in vitro priming of several healthy donors with this epitope of ERV-K-Env did not result in target antigen specificity. These data suggest that the T cell receptor is a poor candidate for targeting this specific ERV-K-Env epitope and has limited potential as a T cell therapy for OC.

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