anti-PD-L1 + anti-TIGIT

**anti-PD-L1 + anti-TIGIT** refers to combination immunotherapy regimens pairing an anti-programmed death-ligand 1 (**PD-L1**) monoclonal antibody, such as **atezolizumab** (Tecentriq) or **zimberelimab**, with an anti-T cell immunoreceptor with Ig and ITIM domains (**TIGIT**) monoclonal antibody, such as **tiragolumab** or **domvanalimab**. These agents block inhibitory immune checkpoints to enhance T cell and NK cell anti-tumor activity: anti-PD-L1 prevents PD-L1 from suppressing T cells via PD-1 interaction, while anti-TIGIT disrupts TIGIT binding to CD155 (PVR) and CD112, relieving suppression on lymphocytes and promoting immune activation. Developed primarily by **Roche/Genentech** (tiragolumab + atezolizumab) and **Gilead/Arcus** (domvanalimab + zimberelimab), the combination has shown superior objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) versus anti-PD-L1 monotherapy in PD-L1-positive metastatic non-small cell lung cancer (NSCLC), particularly with high tumor proportion scores (TPS ≥50%), via mechanisms including myeloid cell activation, tumor-associated macrophage remodeling, and shift of CD8+ T cells from exhausted to memory-like states through Fcγ receptor engagement. Administered intravenously every 3 weeks, it is under evaluation in phase 2/3 trials for NSCLC, hepatocellular carcinoma (HCC), gastric cancer, and other solid tumors, with tiragolumab + atezolizumab receiving FDA Breakthrough Therapy Designation for PD-L1-high NSCLC.

Other names

tiragolumab + atezolizumabdomvanalimab + zimberelimab