期刊
MOLECULAR THERAPY
卷 29, 期 3, 页码 1199-1213出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2020.11.019
关键词
-
资金
- Research Council of Norway [244388, 254817]
- Norwegian Health Region South East [2017075, 2016006]
A novel hTERT-specific TCR sequence, named Radium-4, was isolated from a pancreatic cancer patient vaccinated with a long hTERT peptide, showing promising efficacy in killing malignant tumor cells without toxicity to normal hematopoietic cells. This TCR has a high population coverage and represents an attractive candidate for immunotherapy of solid tumors.
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-4 TCR+ T cells also significantly reduced tumor growth and improved survival in a xenograft mouse model. Since hTERT is a universal cancer antigen, and the very frequently expressed HLA class II molecules presenting the hTERT peptide to this TCR provide a very high (>75%) population coverage, this TCR represents an attractive candidate for immunotherapy of solid tumors.
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