The robust pipeline of anti-TIGIT antibodies suggests promising future of these drugs in the management of cancer. As of now, there are about 15 anti-TIGIT monoclonal antibodies that are being commercially developed including Ociperlimab, Vibostolimab, Domvanalimab, BMS-986207, COM-902, AGEN-1307, and others. The encouraging results from preclinical studies have gained a lot of attention from pharmaceutical giants. The preclinical and clinical data have demonstrated encouraging safety and has shown to significantly enhance the overall survival rate. Recently, the drug Tiragolumab has been granted breakthrough therapy designation by US FDA in combination with Tecentriq (atezolizumab) for the first-line treatment of people with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression with no EGFR or ALK genomic tumor aberrations. By binding to TIGIT, tiragolumab blocks its interaction with a protein called poliovirus receptor (PVR, or CD155) that can suppress the body’s immune response. The most promising anti-TIGIT antibody in development is Tiragolumab, developed by Roche.
Therefore, researchers have developed several drugs targeting TIGIT pathways, which are mainly present in clinical development. In addition, increased TIGIT expression after treatment is associated with disease recurrence. TIGIT has emerged out to be potential target owing to its expression on natural killer cells (NK cells), cytotoxic CD8+ T cells and regulatory T cells (Tregs). Recently, researchers have identified T-cell immunoglobulin and ITIM domain (TIGIT), which is an inhibitory immune checkpoint. To overcome this, researchers have indulged in research activities to identify safer targets which can be blocked or activated to achieve reasonable anti-tumor response with manageable adverse events and can be combined with PD-1/PD-L1 blockers or other immune checkpoint blockers. However, studies have demonstrated that a large fraction of patients did not respond to the treatment, and is also associated with several serious adverse events.
Among all approaches, immune checkpoint inhibitors targeting cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) have been used widely in the treatment of cancers. Numerous immunotherapeutic approaches have been developed which have shown to improve the survival outcomes in cancer patients. Immunotherapy have emerged as the fifth pillar of cancer treatment alongside surgery, radiotherapy, chemotherapy, and targeted therapy.
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