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Updated: Sep 30, 2025
Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity
Published on: November 8, 2016
Development and characterization of anti-galectin-9 antibodies that protect T cells from galectin-9-induced cell
Riyao Yang1, Linlin Sun2, Ching-Fei Li3
1Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Antibody Therapeutics, Inc, Hayward, California, USA.
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.
Insights
Researchers developed novel antibodies that neutralize Galectin-9 (Gal-9), a protein causing T-cell death and immune suppression in tumors. These antibodies protect T cells and enhance their ability to kill cancer cells, offering a new immunotherapy approach.
Area of Science:
- Immunology
- Cancer Biology
- Biotechnology
Background:
- Immune checkpoint inhibitors (ICIs) show success in cancer therapy, but many patients do not respond.
- Galectin-9 (Gal-9) promotes tumor immunosuppression by inducing T-cell death via TIGIT and dectin-1.
- Gal-9 represents a potential therapeutic target for overcoming resistance to current immunotherapies.
Purpose of the Study:
- To develop and characterize novel Gal-9 neutralizing antibodies.
- To evaluate the efficacy of these antibodies in protecting T cells from Gal-9-induced death.
- To assess the potential of Gal-9 blockade in enhancing anti-tumor T-cell activity.
Main Methods:
- Development of high-affinity neutralizing antibodies targeting the N-carbohydrate-recognition domain of human Gal-9.
- Cell-based functional assays to assess T-cell protection from Gal-9.
- T-cell/tumor cell co-culture assays to measure antibody-mediated enhancement of tumor cell killing.
Main Results:
- Two novel antibodies with high affinity for human Gal-9 were successfully developed.
- These antibodies demonstrated significant protection of human T cells against Gal-9-induced cell death.
- The neutralizing antibodies markedly enhanced T-cell-mediated cytotoxicity against tumor cells in co-culture models.
Conclusions:
- Novel Gal-9 neutralizing antibodies effectively inhibit Gal-9 function.
- These antibodies hold promise for novel cancer immunotherapy strategies by restoring T-cell function.
- Targeting Gal-9 represents a potential approach to improve patient responses to cancer immunotherapy.
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