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

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

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)991-998
Number of pages8
JournalMolecular Therapy - Nucleic Acids
Volume18
DOIs
Publication statusPublished - 2019 Dec 6

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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