The Unexpected Benefit of TCR Cross-Reactivity in Cancer Immunotherapy
The ability of T-cell receptors (TCR) to recognize tumor-associated antigens (TAA) is a key driver of adoptive transfer of tumor-infiltrating lymphocyte (TIL) T cells, which can be a highly effective cancer immunotherapy. While it is common knowledge that TCRs are cross-reactive and can bind multipl...
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| Published in: | Cancer research (Chicago, Ill.) Vol. 83; no. 19; pp. 3168 - 3169 |
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| Main Authors: | , |
| Format: | Journal Article |
| Language: | English |
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02-10-2023
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| Abstract | The ability of T-cell receptors (TCR) to recognize tumor-associated antigens (TAA) is a key driver of adoptive transfer of tumor-infiltrating lymphocyte (TIL) T cells, which can be a highly effective cancer immunotherapy. While it is common knowledge that TCRs are cross-reactive and can bind multiple different peptide antigens, this is typically considered an unattractive feature and limitation for TCR-based therapies. In a recent publication in Cell, Dolton and colleagues discover that certain TCRs, isolated from TILs used for successful treatment of melanoma, possess beneficial cross-reactivity by recognizing multiple TAA. Moreover, they elucidate the cumulative value of TCR cross-reactivity on cancer cell eradication and its prospective advantages for targeted cancer immunotherapies. |
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| AbstractList | The ability of T-cell receptors (TCR) to recognize tumor-associated antigens (TAA) is a key driver of adoptive transfer of tumor-infiltrating lymphocyte (TIL) T cells, which can be a highly effective cancer immunotherapy. While it is common knowledge that TCRs are cross-reactive and can bind multiple different peptide antigens, this is typically considered an unattractive feature and limitation for TCR-based therapies. In a recent publication in Cell, Dolton and colleagues discover that certain TCRs, isolated from TILs used for successful treatment of melanoma, possess beneficial cross-reactivity by recognizing multiple TAA. Moreover, they elucidate the cumulative value of TCR cross-reactivity on cancer cell eradication and its prospective advantages for targeted cancer immunotherapies. |
| Author | Reddy, Sai T. Bieberich, Florian |
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| Cites_doi | 10.1038/s41586-023-06081-w 10.7554/eLife.82813 10.1056/NEJMoa2210233 10.1126/science.abl5282 10.1016/j.immuni.2022.09.004 10.1016/j.bbrc.2011.10.092 10.1016/j.immuni.2021.02.014 10.1074/jbc.M111.289488 10.1016/j.cell.2023.06.020 10.1126/science.1129003 |
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| References | Rohaan (2023100207115329500_bib4) 2022; 387 Zhao (2023100207115329500_bib10) 2022; 376 Naghavian (2023100207115329500_bib3) 2023; 617 Bradley (2023100207115329500_bib6) 2023; 12 Chiou (2023100207115329500_bib7) 2021; 54 Wooldridge (2023100207115329500_bib1) 2012; 287 Vazquez-Lombardi (2023100207115329500_bib9) 2022; 55 Dolton (2023100207115329500_bib5) 2023; 186 Narimatsu (2023100207115329500_bib2) 2011; 415 Morgan (2023100207115329500_bib8) 2006; 314 |
| References_xml | – volume: 617 start-page: 807 year: 2023 ident: 2023100207115329500_bib3 article-title: Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma publication-title: Nature doi: 10.1038/s41586-023-06081-w contributor: fullname: Naghavian – volume: 12 start-page: e82813 year: 2023 ident: 2023100207115329500_bib6 article-title: Structure-based prediction of T cell receptor:peptide-MHC interactions publication-title: eLife doi: 10.7554/eLife.82813 contributor: fullname: Bradley – volume: 387 start-page: 2113 year: 2022 ident: 2023100207115329500_bib4 article-title: Tumor-infiltrating lymphocyte therapy or ipilimumab in advanced melanoma publication-title: N Engl J Med doi: 10.1056/NEJMoa2210233 contributor: fullname: Rohaan – volume: 376 start-page: eabl5282 year: 2022 ident: 2023100207115329500_bib10 article-title: Tuning T cell receptor sensitivity through catch bond engineering publication-title: Science doi: 10.1126/science.abl5282 contributor: fullname: Zhao – volume: 55 start-page: 1953 year: 2022 ident: 2023100207115329500_bib9 article-title: High-throughput T cell receptor engineering by functional screening identifies candidates with enhanced potency and specificity publication-title: Immunity doi: 10.1016/j.immuni.2022.09.004 contributor: fullname: Vazquez-Lombardi – volume: 415 start-page: 558 year: 2011 ident: 2023100207115329500_bib2 article-title: Structure-activity relationship of T-cell receptors based on alanine scanning publication-title: Biochem Biophys Res Commun doi: 10.1016/j.bbrc.2011.10.092 contributor: fullname: Narimatsu – volume: 54 start-page: 586 year: 2021 ident: 2023100207115329500_bib7 article-title: Global analysis of shared T cell specificities in human non-small cell lung cancer enables HLA inference and antigen discovery publication-title: Immunity doi: 10.1016/j.immuni.2021.02.014 contributor: fullname: Chiou – volume: 287 start-page: 1168 year: 2012 ident: 2023100207115329500_bib1 article-title: A single autoimmune T cell receptor recognizes more than a million different peptides publication-title: J Biol Chem doi: 10.1074/jbc.M111.289488 contributor: fullname: Wooldridge – volume: 186 start-page: 3333 year: 2023 ident: 2023100207115329500_bib5 article-title: Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy publication-title: Cell doi: 10.1016/j.cell.2023.06.020 contributor: fullname: Dolton – volume: 314 start-page: 126 year: 2006 ident: 2023100207115329500_bib8 article-title: Cancer regression in patients after transfer of genetically engineered lymphocytes publication-title: Science doi: 10.1126/science.1129003 contributor: fullname: Morgan |
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