Antigen-Specific T Cell Immunotherapy Targeting Claudin18.2 in Gastric Cancer

• Published in: Cancers Vol. 14; no. 11; p. 2758
• Main Authors: Xu, Bo, Chen, Fangjun, Zhang, Xin, Wang, Zhongda, Che, Keying, Wu, Nandie, Yu, Lixia, Fan, Xiangshan, Liu, Baorui, Wei, Jia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.06.2022; MDPI
• Subjects: Antibodies; Antigens; Antitumor agents; Cancer therapies; Chemotherapy; Claudin18.2; Clinical trials; Cytokines; Cytotoxicity; Epitopes; Flow cytometry; Gastric cancer; Histocompatibility antigen HLA; Immunogenicity; Immunotherapy; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Membrane proteins; Metastases; Metastasis; Patients; peptide; Peptides; Peripheral blood mononuclear cells; Solid tumors; Tumor necrosis factor-TNF; Beijing China; United States > US; China; Germany; Claudin18.2; peptide; gastric cancer; immunotherapy
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14112758

T cell-based immunotherapy has led to many breakthroughs in the treatment of solid tumors. In this study, we found that membrane protein Claudin18.2 was a promising antigen in T cell-based immunotherapy for gastric cancer (GC). Firstly, we identified five HLA-A*0201- and seven HLA-A*1101-restricted T cell epitopes of Claudin18.2. Peripheral blood mononuclear cells (PBMCs) stimulated by Claudin18.2 peptides showed progressive anti-tumor ability and higher effective cytokine secretion than unstimulated PBMCs in vitro. In total, 81.8% of GC patients were Claudin18.2-positive by immunohistochemical (IHC) detection, and a positive correlation between Claudin18.2 expression and peptide reactivity ( = 0.002) was found. Clinicopathological features analyses demonstrated that Claudin18.2 expression did not correlate with gender, age, stage or Lauren classification. Survival analysis showed that a longer median progression-free survival (mPFS) was not related to peptide reactivity ( = 0.997), but related to a lower Claudin18.2 expression level ( = 0.047). These findings establish a foundation for the clinical application of Claudin18.2 targeted T cell-based immunotherapy in GC.