A DNA Aptamer Targeting Galectin-1 as a Novel Immunotherapeutic Strategy for Lung Cancer

Autor: Yao-Tsung Tsai, Chen-Hsien Liang, Jin-Hsuan Yu, Kuan-Chih Huang, Chia-Hao Tung, Jia-En Wu, Yi-Ying Wu, Chih-Hsien Chang, Tse-Ming Hong, Yuh-Ling Chen
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Molecular Therapy: Nucleic Acids, Vol 18, Iss , Pp 991-998 (2019)
Druh dokumentu: article
ISSN: 2162-2531
DOI: 10.1016/j.omtn.2019.10.029
Popis: Galectin-1 (Gal-1) is a pleiotropic homodimeric β-galactoside-binding protein with a single carbohydrate recognition domain. It has been implicated in several biological processes that are important during tumor progression. Several lines of evidence have indicated that Gal-1 is involved in cancer immune escape and induces T cell apoptosis. These observations all emphasized Gal-1 as a novel target for cancer immunotherapy. Here, we developed a novel Gal-1-targeting DNA aptamer (AP-74 M-545) and demonstrated its antitumor effect by restoring immune function. AP-74 M-545 binds to Gal-1 with high affinity. AP-74 M-545 targets tumors in murine tumor models but suppresses tumor growth only in immunocompetent C57BL/6 mice, not in immunocompromised non-obese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. Immunohistochemistry revealed increased CD4+ and CD8+ T cells in AP-74 M-545-treated tumor tissues. AP-74 M-545 suppresses T cell apoptosis by blocking the binding of Gal-1 to CD45, the main receptor and apoptosis mediator of Gal-1 on T cells. Collectively, our data suggest that the Gal-1 aptamer suppresses tumor growth by blocking the interaction between Gal-1 and CD45 to rescue T cells from apoptosis and restores T cell-mediated immunity. These results indicate that AP-74 M-545 may be a potential strategy for cancer immunotherapy. Keywords: immunotherapy, galectin-1, aptamer, lung cancer
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