Abstract
Antibodies that target immune checkpoint proteins such as programmed cell death protein 1, programmed death ligand 1, and cytotoxic T-lymphocyte–associated antigen 4 in human cancers have achieved impressive clinical success; however, a significant proportion of patients fail to respond to these treatments. Galectin-9 (Gal-9), a β-galactoside-binding protein, has been shown to induce T-cell death and facilitate immunosuppression in the tumor microenvironment by binding to immunomodulatory receptors such as T-cell immunoglobulin and mucin domain–containing molecule 3 and the innate immune receptor dectin-1, suggesting that it may have potential as a target for cancer immunotherapy. Here, we report the development of two novel Gal-9-neutralizing antibodies that specifically react with the N-carbohydrate-recognition domain of human Gal-9 with high affinity. We also show using cell-based functional assays that these antibodies efficiently protected human T cells from Gal-9-induced cell death. Notably, in a T-cell/tumor cell coculture assay of cytotoxicity, these antibodies significantly promoted T cell-mediated killing of tumor cells. Taken together, our findings demonstrate potent inhibition of human Gal-9 by neutralizing antibodies, which may open new avenues for cancer immunotherapy.
Original language | English (US) |
---|---|
Article number | 101821 |
Journal | Journal of Biological Chemistry |
Volume | 298 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2022 |
Keywords
- TIM-3
- cancer biology
- galectin-9
- immune checkpoint
- immunotherapy
- monoclonal antibody
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
MD Anderson CCSG core facilities
- Advanced Technology Genomics Core
- Research Animal Support Facility
- Cytogenetics and Cell Authentication Core
- Monoclonal Antibody Facility