Limited Immunogenicity of an HLA-A*03:01-restricted Epitope of Erv-k-env in Non-hiv-1 Settings: Implications for Adoptive Cell Therapy in Cancer.

Repetitive elements (REs) 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 RE ERV-K is frequently expressed by tumor cells. Here we determined whether the targeting of a previously identified immunogenic epitope in the envelope gene (env) of ERV-K resulted in target antigen specificity in non-HIV-1 settings. 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, these transduced T cells were not specific for HLA-A*03:01 + OC cells nor for the cognate peptide in HLA-matched systems from multiple healthy donors. These data suggest that the ERV-K-Env epitope recognized by this T cell receptor is of low immunogenicity and has limited potential as a T cell target for OC.
Competing Interests: Additional Declarations: Competing interest reported. Erin E. Grundy: no such conflicts exist Lauren C. Shaw: no such conflicts exist Daniel J. Powell Jr.: no such conflicts exist Mario Ostrowski: no such conflicts exist R. Brad Jones: no such conflicts exist C. Russell Y. Cruz: no such conflicts exist Heather Gordish-Dressman: no such conflicts exist Catherine M. Bollard: no such conflicts exist Katherine B. Chiappinelli: consultant for Rome Therapeutics DISCLOSURES & COMPETING INTERESTS KBC is a consultant for Rome Therapeutics.