期刊
CANCER LETTERS
卷 573, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2023.216366
关键词
TCR T-cell therapy; Tumor antigen; Pancreatic adenocarcinoma; Epitope-based immunotherapy; Mass spectrometry
类别
Researchers have identified a natural CD8+ T-cell epitope, LAMC2203211, in pancreatic ductal adenocarcinoma (PDAC) using mass spectrometry analysis. This epitope induces specific immune responses and suppresses the growth of PDAC cells. This study provides a new approach for developing PDAC immunotherapy strategies based on this epitope.
Tumor antigens are crucial targets for T-cell-based therapy to induce tumor-specific rejection. However, identifying pancreatic ductal adenocarcinoma (PDAC)-specific T-cell epitopes has been challenging. Using advanced mass spectrometry (MS) analysis, we previously identified cancer-associated, class I MHC-bound epitopes shared by multiple PDAC patients with different HLA-A types. Here, we investigated one of these epitopes, LAMC2203211, a naturally occurring nonmutated epitope on the LAMC2 protein. Following stimulation with the LAMC2203211 peptide, we cloned T-cell receptors (TCRs) and transduced them into the Jurkat human T-cell line using a lentiviral vector. We found that Jurkat cells expressing LAMC2203-211-specific TCRs resulted in potent, LAMC2 specific, in vitro cytotoxic effects on PDAC cells. Furthermore, in mice that harbored either subcutaneously or orthotopically implanted tumors originating from both HLA-A allele-matched and unmatched PDAC patients, tumor growth was suppressed in a LAMC2-dependent manner following the infusion of LAMC2-targeting T cells. We have therefore developed a LAMC2-specific TCR-based T-cell therapy strategy likely suitable for many PDAC patients. This is the first study to adopt MS analysis to identify natural CD8+ T-cell epitopes in PDAC that could potentially serve as targets for PDAC immunotherapy.
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