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

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

doi:10.1186/s13100-024-00333-w

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

Mob DNA. 2024 Oct 9;15(1):19. doi: 10.1186/s13100-024-00333-w.

Authors

Erin E Grundy^{1

2

3}, Lauren C Shaw⁴, Loretta Wang^{1

2}, Abigail V Lee^{1

2

3}, James Castro Argueta⁵, Daniel J Powell Jr⁴, Mario Ostrowski⁶, R Brad Jones⁷, C Russell Y Cruz^{2

3

8}, Heather Gordish-Dressman^{5

9}, Nicole P Chappell², Catherine M Bollard^{2

3

8}, Katherine B Chiappinelli^{10

11

12}

Affiliations

¹ Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
² The George Washington University Cancer Center, Washington, DC, USA.
³ The Integrated Biomedical Sciences at the George Washington University, Washington, DC, USA.
⁴ Department of Pathology and Laboratory Medicine, Center for Cellular Immunotherapies, Perelman School of Medicine, Ovarian Cancer Research Center, The University of Pennsylvania, Philadelphia, PA, USA.
⁵ The George Washington School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
⁶ Department of Medicine, University of Toronto, Toronto, Canada.
⁷ Weill Cornell Medicine Graduate School of Medical Sciences, New York, NY, USA.
⁸ Center for Cancer and Immunology, , Children's National Hospital, Washington, DC, United States.
⁹ The Center for Translational Research, Children's National Hospital, Washington, DC, USA.
¹⁰ Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA. kchiapp1@email.gwu.edu.
¹¹ The George Washington University Cancer Center, Washington, DC, USA. kchiapp1@email.gwu.edu.
¹² The Integrated Biomedical Sciences at the George Washington University, Washington, DC, USA. kchiapp1@email.gwu.edu.

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.

Keywords: Endogenous retroviruses; Immunotherapy; T cell receptor; Transposable elements; Tumor immunology.

Abstract

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