Monoclonal Antibodies Targeting TIM-3 to Block Binding to the Human TIM-3 Receptor

Project Overview

• TIM-3, a transmembrane receptor protein, is known to inhibit the immune response and high expression of the TIM-3 receptor on T cells in human cancers and HIV, and plays a crucial role in T cell exhaustion that occurs with these chronic conditions.
• There is a pressing need for new molecules that can regulate TIM-3 function and reinvigorate immune responses.
• Scientists at Dana-Farber have developed monoclonal antibodies (mAb) that target human TIM-3 with high specificity.
• Dana-Farber Cancer Institute is looking for the right partner with an interest in licensing these assets for further development into new therapeutics or vaccines.

Technology

The activation of CD4+ T helper cells leads to the development of various effector populations, including T helper 1 (Th1) and T helper 1 (Th2), which have distinct roles in the production of cytokines implicated in immune responses, autoimmune diseases, asthma, and allergies.

TIM-3, a transmembrane receptor protein, is expressed on Th1 and CD8+ T cells and is upregulated on activated, effector T cells. TIM-3 can also be expressed on myeloid cell populations such as brain microglia. TIM-3 is known to inhibit the immune response and high expression of the TIM-3 receptor on T cells is observed in human cancers and HIV and plays a crucial role in T cell exhaustion that occurs with these chronic conditions.

Current immunotherapies often fall short in effectively managing these conditions and do not adequately address the modulation of TIM-3, leaving a gap in treatment efficacy for diseases characterized by immune suppression. Thus, there is a pressing need for new molecules that can regulate TIM-3 function and reinvigorate immune responses.

Research from Dr. Gordon Freeman’s team at the Dana-Farber Cancer Institute has led to the development of monoclonal antibodies (mAb) that target human TIM-3 with high specificity. Among these, mAb T3H.22C1 demonstrates high affinity binding to TIM-3 and cross-reactivity with cynomolgus TIM-3, making it ideal for preclinical trials in primate models. This antibody effectively blocks TIM-3’s binding to phosphatidylserine, a key ligand, thereby potentially reversing T cell exhaustion. In laboratory assays, T3H.22C1 has shown promising results. It enhances IFN-gamma and TNF-alpha secretion in T cells, indicating a reinvigoration of immune activity. Additionally, it boosts the cytotoxic activity of NK cells, which is crucial for targeting cancer cells. These effects are significant improvements over current therapies, which often fail to sustain long-term immune activation. Another monoclonal antibody, T3H.23D8, is effective in immunohistochemistry and western blot applications, allowing for precise identification of TIM-3 expressing cells in tissues. By specifically targeting and modulating TIM-3 activity, these antibodies offer a promising approach to overcoming immune suppression in chronic diseases and are applicable to both diagnostic and therapeutic monitoring purposes.

Further Details:

1. Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked TIM gene family, Freeman, DeKruyff, et al. Nature Immunol. 2001, _2(12):_1109-16. DOI: 10.1038/ni739
2. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Freeman, Kuchroo, et al. Nature. 2002, 415(6871):536-41. DOI: 10.1038/415536a
3. Co-operation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Freeman, Ahmed, et al. Proc Natl Acad Sci USA. 2010, 107(33):14733-8. DOI: 10.1073/pnas.1009731107
4. Immune checkpoint TIM-3 regulates microglia and Alzheimer’s disease, Kimura, Kuchroo, et al. Nature. 2025, 641(8063):718-731. DOI: 10.1038/s41586-025-08852-z

Applications

The monoclonal antibodies targeting TIM-3 have broad potential applications, including:

Diagnostic Tools: Identifying TIM-3 expression in various tissues for better disease characterization.Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit.

Cancer Therapy: Enhancing immune response against tumors by reversing T cell exhaustion.

Infectious Diseases: Improving immune function in chronic infections like HIV.

Autoimmune Disorders: Modulating immune responses in diseases such as Crohn’s disease and glomerulonephritis.

Alzheimer’s Disease: Improving cognitive function in Alzheimer’s disease by therapeutically targeting microglial TIM-3.

Opportunities

Dana-Farber Cancer Institute is looking for the right partner with an interest in licensing these assets for further development into new therapeutics or vaccines.

Team Members

Gordon Freeman, PhD

Professor of Medicine, Dana-Farber and Harvard Medical School

Gordon's Bio