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
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.
Authors
- Erin E. Grundy (ORCID: https://orcid.org/0000-0001-7094-1461)
- Catherine M. Bollard (ORCID: https://orcid.org/0000-0001-5140-9090)
- Carolina Colli Cruz (ORCID: https://orcid.org/0000-0001-7065-3769)
- Katherine B. Chiappinelli (ORCID: https://orcid.org/0000-0001-9241-9105)
- Loretta Wang
- R. Brad Jones
- Daniel J. Powell (ORCID: https://orcid.org/0000-0002-5966-8908)
- Mario Ostrowski (ORCID: https://orcid.org/0000-0002-7369-1936)
- Lauren Shaw (ORCID: https://orcid.org/0000-0002-4104-2261)
- Heather Gordish‐Dressman (ORCID: https://orcid.org/0000-0002-2330-5427)
- Abigail V. Lee
- Nicole P. Chappell
- James Castro Argueta
Institutions
- Children's National (US)
- University of Toronto (CA)
- George Washington University (US)
- Cornell University (US)
- Center for Cancer and Blood Disorders (US)
- Cancer Research Center (US)
- Weill Cornell Medicine (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Mobile DNA
- Published
- 2024-10-09
- DOI
- https://doi.org/10.1186/s13100-024-00333-w
- Citations
- 2
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.48
Funders
- U.S. Department of Defense
- Cosmos Club Foundation
- Children's National Hospital
- National Institutes of Health