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Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy
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(2023) Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy. Cell, 186 (16). 3333-3349.e27. doi:10.1016/j.cell.2023.06.020 ISSN 0092-8674.
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Official URL: http://doi.org/10.1016/j.cell.2023.06.020
Abstract
The T cells of the immune system can target tumors and clear solid cancers following tumor-infiltrating lymphocyte (TIL) therapy. We used combinatorial peptide libraries and a proteomic database to reveal the antigen specificities of persistent cancer-specific T cell receptors (TCRs) following successful TIL therapy for stage IV malignant melanoma. Remarkably, individual TCRs could target multiple different tumor types via the HLA A∗02:01-restricted epitopes EAAGIGILTV, LLLGIGILVL, and NLSALGIFST from Melan A, BST2, and IMP2, respectively. Atomic structures of a TCR bound to all three antigens revealed the importance of the shared x-x-x-A/G-I/L-G-I-x-x-x recognition motif. Multi-epitope targeting allows individual T cells to attack cancer in several ways simultaneously. Such “multipronged” T cells exhibited superior recognition of cancer cells compared with conventional T cell recognition of individual epitopes, making them attractive candidates for the development of future immunotherapies.
| Item Type: | Journal Article | ||||||||||||||||||||||||
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| Subjects: | Q Science > QR Microbiology > QR180 Immunology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Mathematics | ||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Cancer -- Immunotherapy, Antineoplastic agents -- Therapeutic use, T cells -- Receptors, Immunogenetics, HLA histocompatibility antigens, Tumors -- Immunological aspects, Lymphocytes | ||||||||||||||||||||||||
| Journal or Publication Title: | Cell | ||||||||||||||||||||||||
| Publisher: | Cell Press | ||||||||||||||||||||||||
| ISSN: | 0092-8674 | ||||||||||||||||||||||||
| Official Date: | 3 August 2023 | ||||||||||||||||||||||||
| Dates: |
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| Volume: | 186 | ||||||||||||||||||||||||
| Number: | 16 | ||||||||||||||||||||||||
| Page Range: | 3333-3349.e27 | ||||||||||||||||||||||||
| DOI: | 10.1016/j.cell.2023.06.020 | ||||||||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||
| Date of first compliant deposit: | 20 September 2023 | ||||||||||||||||||||||||
| Date of first compliant Open Access: | 20 September 2023 | ||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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