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The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review

T-cell receptor–engineered T-cell therapy and chimeric antigen receptor T-cell therapy are 2 types of adoptive T-cell therapy that genetically modify natural T cells to treat cancers. Although chimeric antigen receptor T-cell therapy has yielded remarkable efficacy for hematological malignancies of...

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Autores principales: Zhang, Jianxiang, Wang, Lingyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391541/
https://www.ncbi.nlm.nih.gov/pubmed/30798772
http://dx.doi.org/10.1177/1533033819831068
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author Zhang, Jianxiang
Wang, Lingyu
author_facet Zhang, Jianxiang
Wang, Lingyu
author_sort Zhang, Jianxiang
collection PubMed
description T-cell receptor–engineered T-cell therapy and chimeric antigen receptor T-cell therapy are 2 types of adoptive T-cell therapy that genetically modify natural T cells to treat cancers. Although chimeric antigen receptor T-cell therapy has yielded remarkable efficacy for hematological malignancies of the B-cell lineages, most solid tumors fail to respond significantly to chimeric antigen receptor T cells. T-cell receptor–engineered T-cell therapy, on the other hand, has shown unprecedented promise in treating solid tumors and has attracted growing interest. In order to create an unbiased, comprehensive, and scientific report for this fast-moving field, we carefully analyzed all 84 clinical trials using T-cell receptor–engineered T-cell therapy and downloaded from ClinicalTrials.gov updated by June 11, 2018. Informative features and trends were observed in these clinical trials. The number of trials initiated each year is increasing as expected, but an interesting pattern is observed. NY-ESO-1, as the most targeted antigen type, is the target of 31 clinical trials; melanoma is the most targeted cancer type and is the target of 33 clinical trials. Novel antigens and underrepresented cancers remain to be targeted in future studies and clinical trials. Unlike chimeric antigen receptor T-cell therapy, only about 16% of the 84 clinical trials target against hematological malignancies, consistent with T-cell receptor–engineered T-cell therapy’s high potential for solid tumors. Six pharma/biotech companies with novel T-cell receptor–engineered T-cell ideas and products were examined in this review. Multiple approaches have been utilized in these companies to increase the T-cell receptor’s affinity and efficiency and to minimize cross-reactivity. The major challenges in the development of the T-cell receptor–engineered T-cell therapy due to tumor microenvironment were also discussed here.
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spelling pubmed-63915412019-03-04 The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review Zhang, Jianxiang Wang, Lingyu Technol Cancer Res Treat Review T-cell receptor–engineered T-cell therapy and chimeric antigen receptor T-cell therapy are 2 types of adoptive T-cell therapy that genetically modify natural T cells to treat cancers. Although chimeric antigen receptor T-cell therapy has yielded remarkable efficacy for hematological malignancies of the B-cell lineages, most solid tumors fail to respond significantly to chimeric antigen receptor T cells. T-cell receptor–engineered T-cell therapy, on the other hand, has shown unprecedented promise in treating solid tumors and has attracted growing interest. In order to create an unbiased, comprehensive, and scientific report for this fast-moving field, we carefully analyzed all 84 clinical trials using T-cell receptor–engineered T-cell therapy and downloaded from ClinicalTrials.gov updated by June 11, 2018. Informative features and trends were observed in these clinical trials. The number of trials initiated each year is increasing as expected, but an interesting pattern is observed. NY-ESO-1, as the most targeted antigen type, is the target of 31 clinical trials; melanoma is the most targeted cancer type and is the target of 33 clinical trials. Novel antigens and underrepresented cancers remain to be targeted in future studies and clinical trials. Unlike chimeric antigen receptor T-cell therapy, only about 16% of the 84 clinical trials target against hematological malignancies, consistent with T-cell receptor–engineered T-cell therapy’s high potential for solid tumors. Six pharma/biotech companies with novel T-cell receptor–engineered T-cell ideas and products were examined in this review. Multiple approaches have been utilized in these companies to increase the T-cell receptor’s affinity and efficiency and to minimize cross-reactivity. The major challenges in the development of the T-cell receptor–engineered T-cell therapy due to tumor microenvironment were also discussed here. SAGE Publications 2019-02-24 /pmc/articles/PMC6391541/ /pubmed/30798772 http://dx.doi.org/10.1177/1533033819831068 Text en © The Author(s) 2019 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Review
Zhang, Jianxiang
Wang, Lingyu
The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review
title The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review
title_full The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review
title_fullStr The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review
title_full_unstemmed The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review
title_short The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review
title_sort emerging world of tcr-t cell trials against cancer: a systematic review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391541/
https://www.ncbi.nlm.nih.gov/pubmed/30798772
http://dx.doi.org/10.1177/1533033819831068
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