Combined Therapy of PD-1 and TIGIT

Introduction to Combined Therapy

In multiple cancers, the overexpression of inhibitory checkpoint molecules and their ligands has been demonstrated to escape immune surveillance. In recent years, the single checkpoint blockade and combined therapies present great potentials in both preclinical and clinical settings. More importantly, combination therapy can regulate the immune system in a variety of ways, which can significantly improve the efficacy and survival rate.

Combined Therapy of PD-1 and TIGIT in GBM

Glioblastoma (GBM) is an aggressive disease with high rates of morbidity and mortality. The current treatment always results in median survival of fewer than two years. In this case, immune checkpoint inhibitors are one of the most important immunotherapeutic agents to modulate the host immune response for cancer treatment.

TIGIT is a novel checkpoint inhibitor that works in cancer immunity. Clinically, overexpression of TIGIT has been tested in patients with GBM, suggesting that the TIGIT pathway might be the valuable target. Besides, PD-1 is the classical immune checkpoint against multiple cancers. In this case, the recent research sought to determine the effect of PD-1/TIGIT combination therapy in a murine GBM model. Compared with anti-PD-1 monotherapy and anti-TIGIT monotherapy groups, the combined therapy results in increased both CD8⁺ and CD4⁺ T cells in mouse models. The previous studies showed that tumor-infiltrating dendritic cells (TIDCs) might promote a suppressive microenvironment according to the inhibition of T cell immunity. Compared with the combination group, the control group always presents higher infiltration of DCs (CD11b⁺CD11c⁺cells). In conclusion, the combination of anti-PD-1 with anti-TIGIT is an effective treatment strategy to improve overall survival against murine GBM.

Fig.1 Simplified overview of multiple co-stimulatory and inhibitory immune checkpoint molecules that regulate T cell responses and their ligand-receptor interactions. (Wang, 2019)

Services at Creative Biolabs

Creative Biolabs is a leading service provider that focuses on combined therapy against multiple cancers. Based on our advanced drug discovery platform and extensive experience, now we can provide a series of services for our clients all over the world, including but not limited to:

• Immune Checkpoint Antibody Development
• Immune Checkpoint Targeted Small Molecule Drug Development
• Immune Checkpoint Assays
• Custom Immune Checkpoint Protein Development
• Immune Checkpoint Targeted Peptide Development
• Preclinical Research for Immune Checkpoint Drugs

If you are interested in our services, please do not hesitate to contact us for more detailed information.

Reference

1. Wang, M.; et al. Immune checkpoint blockade and its combination therapy with small-molecule inhibitors for cancer treatment. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2019, 1871(2): 199-224.

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