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

Authors

Erin E. Grundy, Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
Lauren C. Shaw, 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.
Loretta Wang, Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
Abigail V. Lee, Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
James Castro Argueta, The George Washington School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
Daniel J. Powell, 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.
Mario Ostrowski, Department of Medicine, University of Toronto, Toronto, Canada.
R Brad Jones, Weill Cornell Medicine Graduate School of Medical Sciences, New York, NY, USA.
C Russell Cruz, The George Washington University Cancer Center, Washington, DC, USA.
Heather Gordish-Dressman, The George Washington School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
Nicole P. Chappell, The George Washington University Cancer Center, Washington, DC, USA.
Catherine M. Bollard, The George Washington University Cancer Center, Washington, DC, USA.
Katherine B. Chiappinelli, Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA. kchiapp1@email.gwu.edu.

Document Type

Journal Article

Publication Date

10-9-2024

Journal

Mobile DNA

Volume

15

Issue

1

DOI

10.1186/s13100-024-00333-w

Keywords

Endogenous retroviruses; Immunotherapy; T cell receptor; Transposable elements; Tumor immunology

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.

APA Citation

Grundy, Erin E.; Shaw, Lauren C.; Wang, Loretta; Lee, Abigail V.; Argueta, James Castro; Powell, Daniel J.; Ostrowski, Mario; Jones, R Brad; Cruz, C Russell; Gordish-Dressman, Heather; Chappell, Nicole P.; Bollard, Catherine M.; and Chiappinelli, Katherine B., "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" (2024). GW Authored Works. Paper 5856.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5856

Department

Pediatrics