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

Autor:	Dillard P; Department of Cellular Therapy, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway., Köksal H; Department of Cellular Therapy, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway., Maggadottir SM; Department of Cellular Therapy, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway., Winge-Main A; Department of Cellular Therapy, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway., Pollmann S; Department of Cellular Therapy, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway., Menard M; Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway., Myhre MR; Department of Cellular Therapy, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway., Mælandsmo GM; Department of Tumor Biology, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway., Flørenes VA; Department of Pathology, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway., Gaudernack G; Department of Cancer Immunology, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway., Kvalheim G; Department of Cellular Therapy, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway., Wälchli S; Department of Cellular Therapy, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway. Electronic address: sebastw@rr-research.no., Inderberg EM; Department of Cellular Therapy, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway. Electronic address: elsin@rr-research.no.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2021 Mar 03; Vol. 29 (3), pp. 1199-1213. Date of Electronic Publication: 2020 Nov 17.
DOI:	10.1016/j.ymthe.2020.11.019
Abstrakt:	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. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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