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,
Mario Ostrowski,
R. Brad Jones,
C. Russell Y. Cruz,
Heather Gordish-Dressman,
Nicole P. Chappell,
Catherine M. Bollard,
Katherine B. Chiappinelli
Affiliations
Erin E. Grundy
Department of Microbiology, Immunology and Tropical Medicine, The George Washington University
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
Loretta Wang
Department of Microbiology, Immunology and Tropical Medicine, The George Washington University
Abigail V. Lee
Department of Microbiology, Immunology and Tropical Medicine, The George Washington University
James Castro Argueta
The George Washington School of Medicine and Health Sciences, The George Washington University
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
Mario Ostrowski
Department of Medicine, University of Toronto
R. Brad Jones
Weill Cornell Medicine Graduate School of Medical Sciences
C. Russell Y. Cruz
The George Washington University Cancer Center
Heather Gordish-Dressman
The George Washington School of Medicine and Health Sciences, The George Washington University
Nicole P. Chappell
The George Washington University Cancer Center
Catherine M. Bollard
The George Washington University Cancer Center
Katherine B. Chiappinelli
Department of Microbiology, Immunology and Tropical Medicine, The George Washington University
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.
