Targeting Telomerase with an HLA Class II-Restricted TCR for Cancer Immunotherapy.

ABSTRACT: T cell receptor (TCR)-engineered T cell therapy is a promising cancer treatment approach. Human telomerase reverse transcriptase (hTERT) is overexpressed in the majority of tumors and a potential target for adoptive cell therapy. We isolated a novel hTERT-specific TCR sequence, named Radium-4, from a clinically responding pancreatic cancer patient vaccinated with a long hTERT peptide. Radium-4 TCR-redirected primary CD4⁺ and CD8⁺ T cells demonstrated in vitro efficacy, producing inflammatory cytokines and killing hTERT⁺ melanoma cells in both 2D and 3D settings, as well as malignant, patient-derived ascites cells. Importantly, T cells expressing Radium-4 TCR displayed no toxicity against bone marrow stem cells or mature hematopoietic cells. Notably, Radium-

SUBMITTER: Dillard P 

PROVIDER: S-EPMC7934585 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature