Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy
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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.
Original language | English |
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Journal | Cell |
Volume | 186 |
Issue number | 16 |
Pages (from-to) | 3333-3349.e27 |
Number of pages | 45 |
ISSN | 0092-8674 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
Publisher Copyright:
© 2023 The Authors
- cancer immunotherapy, HLA class I, peptide-HLA, T cell receptor, TCR, TCR-T, TIL therapy, TILs, tumor-infiltrating lymphocytes
Research areas
ID: 370796382