2023-07-24 カーディフ大学
◆従来の考えでは、個々のキラーT細胞はがん細胞上の1つのターゲットしか見ないと考えられていましたが、新しい「多面的」細胞は異なり、複数の方法でがんを攻撃できます。
◆研究チームは、末期の固形がん患者にTIL療法を行い、成功したT細胞を追跡しました。そして、これらのキラーT細胞ががん細胞と正常細胞をどのように区別しているかを特定しました。これらの発見は、将来の免疫療法の開発に対する重要な進展であり、多面的T細胞ががんの治療において有望な役割を果たす可能性が示唆されています。
<関連情報>
- https://www.cardiff.ac.uk/news/view/2734440-superior-t-cell-discovered-in-cancer-survivors
- https://www.cell.com/cell/fulltext/S0092-8674(23)00696-7
個々のT細胞受容体が複数の腫瘍関連抗原を標的とすることで、がん免疫療法が成功する Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy
Garry Dolton ,Cristina Rius,Aaron Wall,Barbara Szomolay,Valentina Bianchi,Sarah A.E. Galloway,Md Samiul Hasan,Théo Morin,Marine E. Caillaud,Hannah L. Thomas,Sarah Theaker,Li Rong Tan,Anna Fuller,Katie Topley,Mateusz Legut,Meriem Attaf,Jade R. Hopkins,Enas Behiry,Joanna Zabkiewicz,Caroline Alvares,Angharad Lloyd,Amber Rogers,Peter Henley,Christopher Fegan,Oliver Ottmann,Stephen Man,Michael D. Crowther,Marco Donia,Inge Marie Svane,David K. Cole,Paul E. Brown,Pierre Rizkallah,Andrew K. Sewell
Cell Published:July 24, 2023
DOI:https://doi.org/10.1016/j.cell.2023.06.020
Highlights
•Individual T cells from successful immunotherapy recognize multiple cancer types
•A deciphering pipeline identifies new epitopes recognized by these “orphan” T cells
•Single T cells recognize multiple, different tumor-associated antigens simultaneously
•“Multipronged” TCRs exhibit superior cancer recognition compared with monospecific TCRs
Summary
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.
