# 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

## TL;DR

This study shows that a specific T cell receptor targeting an ERV-K-Env epitope has limited effectiveness in non-HIV-1 cancer settings like ovarian cancer.

## Contribution

The study reveals the limited immunogenicity of an HLA-A*03:01-restricted ERV-K-Env epitope in non-HIV-1 contexts.

## Key findings

- Transduced T cells showed antigen specificity only with HLA-A*03:01 B lymphoblastoid cells.
- T cells were not specific for HLA-A*03:01+ ovarian cancer cells or cognate peptides in HLA-matched systems.
- The epitope has low immunogenicity and limited potential for adoptive cell therapy in ovarian cancer.

## Abstract

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.