TIGIT antibodies represent an innovative development in cancer treatment. These treatments are designed to empower the body’s own immune system to recognize and eliminate cancerous cells. By precisely targeting specific pathways, TIGIT antibodies aim to unleash the immune system’s natural ability to combat disease. This approach holds promise for enhancing current cancer treatment strategies and improving patient outcomes.
Understanding TIGIT and Its Immune Role
TIGIT, or T-cell immunoreceptor with immunoglobulin and ITIM domains, is a protein found on the surface of certain immune cells, including T cells and natural killer (NK) cells. It functions as an “immune checkpoint,” regulating the immune response to prevent overactivity and maintain immune balance. Cancer cells, however, exploit this natural braking mechanism by expressing high levels of TIGIT’s binding partners, known as ligands, such as PVR (also called CD155) and CD112. When TIGIT on immune cells binds to these ligands on cancer cells or within the tumor environment, it sends inhibitory signals. These signals dampen T cell and NK cell activity, allowing cancer cells to evade detection and destruction, contributing to an immunosuppressive environment within tumors.
How TIGIT Antibodies Function
A TIGIT antibody is designed to bind to the TIGIT protein on immune cells, blocking its interaction with ligands like PVR found on cancer cells or other immune cells. This blocking action “releases the brakes” on the immune system. When the inhibitory signals from TIGIT are disrupted, T cells and NK cells become activated and proliferate, enhancing their ability to recognize and attack cancer cells. Additionally, TIGIT antibodies can reduce the suppressive activity of regulatory T cells (Tregs), which are immune cells that often contribute to the tumor’s ability to evade immune surveillance. Some TIGIT antibodies may also directly kill TIGIT-expressing tumor cells and enhance the production of cytokines, signaling molecules that further amplify the immune response.
Current Applications and Clinical Progress
TIGIT antibodies are currently undergoing extensive investigation for their potential in treating various cancers, including non-small cell lung cancer (NSCLC), melanoma, and colorectal cancer. Clinical trials are progressing through different phases, from early-stage Phase I/II trials focused on safety and dosing, to later-stage Phase III trials evaluating efficacy. Over 50 anti-TIGIT antibodies are in clinical development, with several having advanced into Phase III trials. Initial results from some trials have shown promising outcomes, with patients experiencing tumor shrinkage and extended progression-free survival, particularly in NSCLC. For instance, in one study, the combination of an anti-TIGIT treatment (tiragolumab) with an anti-PD-L1 therapy (atezolizumab) in NSCLC patients resulted in a higher objective response rate compared to atezolizumab alone.
Combining TIGIT Antibodies for Enhanced Treatment
The strategy of combining TIGIT antibodies with other immunotherapies, particularly PD-1/PD-L1 inhibitors, is a key area of focus. PD-1/PD-L1 inhibitors, like pembrolizumab and nivolumab, target a different immune checkpoint pathway that also acts as a brake on immune cells. By simultaneously blocking both the TIGIT and PD-1/PD-L1 pathways, researchers aim to achieve a more robust and sustained anti-tumor immune response. This combination leverages the concept of synergistic effects, where the combined action of two therapies is greater than their individual effects. For example, dual blockade of TIGIT and PD-1 has been shown to increase the expansion and function of tumor antigen-specific CD8+ T cells and promote tumor rejection in preclinical models, holding potential to improve treatment outcomes, overcome resistance mechanisms, and offer new hope for patients who may not respond to single-agent immunotherapies.