BCL2A1 neoepitope-elicited cytotoxic T lymphocytes are a promising individualized immunotherapy of pancreatic cancer

• Published in: Journal of leukocyte biology Vol. 116; no. 3; p. 601
• Main Authors: Lin, Shengzhe, Hong, Jingwen, Wu, Suxin, Zhu, Chenlu, Liu, Fang, Lin, Wansong, Cai, Xinran, Ye, Yunbin, Chen, Yanling
• Format: Journal Article
• Language: English
• Published: England 02.09.2024
• Subjects: Antigens, Neoplasm - immunology; Cell Line, Tumor; Dendritic Cells - immunology; Epitopes - immunology; Female; HLA-A2 Antigen - immunology; Humans; Immunotherapy - methods; Male; Middle Aged; Minor Histocompatibility Antigens; Mutation; Pancreatic Neoplasms - immunology; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Precision Medicine; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - immunology; T-Lymphocytes, Cytotoxic - immunology; neoantigen; pancreatic cancer; cytotoxic T lymphocytes; BCL2A1
• ISSN: 1938-3673
• DOI: 10.1093/jleuko/qiae092

Conventional treatments have shown a limited efficacy for pancreatic cancer, and immunotherapy is an emerging option for treatment of this highly fatal malignancy. Neoantigen is critical to improving the efficacy of tumor-specific immunotherapy. The cancer and peripheral blood specimens from an HLA-A0201-positive pancreatic cancer patient were subjected to next-generation sequencing, and bioinformatics analyses were performed to screen high-affinity and highly stable neoepitopes. The activation of cytotoxic T lymphocytes (CTLs) by dendritic cells (DCs) loaded with mutBCL2A111-20 neoepitope targeting a BCL2A1 mutant epitope was investigated, and the cytotoxicity of mutBCL2A111-20 neoepitope-specific CTLs to pancreatic cancer cells was evaluated. The mutBCL2A111-20 neoepitope was found to present a high immunogenicity and induce CTLs activation and proliferation, and these CTLs were cytotoxic to mutBCL2A111-20 neoepitope-loaded T2 cells and pancreatic cancer PANC-1-Neo and A2-BxPC-3-Neo cells that overexpressed mutBCL2A111-20 neoepitopes, appearing to be a targeting neoepitope specificity. In addition, high BCL2A1 expression correlated with a low 5-yr progression-free interval among pancreatic cancer patients. Our findings provide experimental supports to individualized T cell therapy targeting mutBCL2A111-20 neoepitopes, and provide an option of immunotherapy for pancreatic cancer.