Tiragolumab

概览

Tiragolumab is an investigational anti-TIGIT monoclonal antibody being developed for cancer immunotherapy. In the phase II CITYSCAPE trial, tiragolumab combined with atezolizumab demonstrated significantly improved objective response rates and progression-free survival in non-small cell lung cancer (NSCLC) compared to PD-1 inhibition alone. Tiragolumab is currently advancing through phase III clinical trials.

作用机制

Tiragolumab is a monoclonal antibody that targets TIGIT (T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain), an immune checkpoint receptor broadly expressed on T cells, natural killer (NK) cells, and regulatory T cells (Tregs). TIGIT exerts immunosuppressive effects primarily through competitive engagement with ligands CD155 and CD112, which interrupts the activating signals mediated by CD226, a co-stimulatory receptor required for robust T and NK cell cytotoxic activity. By blocking TIGIT, tiragolumab prevents this competitive inhibition, thereby restoring CD226-mediated co-stimulatory signaling and enhancing anti-tumor immunity. Dual blockade of TIGIT and PD-1 pathways demonstrates immunologic synergy, attributed to TIGIT blockade's capacity to reverse T-cell exhaustion and mitigate NK cell depletion, effectively overcoming mechanisms of PD-1 resistance.

适应症

Tiragolumab is being investigated in combination with atezolizumab for the treatment of non-small cell lung cancer (NSCLC). In the phase II CITYSCAPE trial, the combination demonstrated significantly improved objective response rates and progression-free survival compared to PD-1 inhibition alone.

• Non-small cell lung cancer