Looking back on 2023, Merck & Co., Inc. and Roche Holding AG released less-than-impressive findings on their anti-TIGIT combinations in non-small cell lung cancer (NSCLC). The bright spot last year was Arcus Biosciences, Inc. and Gilead Sciences, Inc.’s anti-TIGIT/anti-programmed cell death ligand 1 (PD-L1) coformulation in gastric cancer, which showed greater efficacy than the standard of care for gastric cancers, particularly in high-PD-L1 expressers.
“Whilst it seems hope is not lost for the TIGIT drug class, Phase II data will not be sufficient to restore the initial excitement around this class
The Initial Hype
Co-blockade of the T-cell immunoreceptor with Ig and ITIM domains – TIGIT, for short – was initially touted as a way to widen the pool of candidates that could benefit from checkpoint inhibition, potentially improving the efficacy of anti-PD-1/PD-L1 drugs. The degree of TIGIT expression on tumor-infiltrating NK cells has been linked to tumor progression and to functional exhaustion of NK cells. Thus, combining TIGIT blockage with PD-1 blockade (and, in some trials, other immunotherapies) could prevent or reverse T-cell exhaustion and boost immune-mediated tumor rejection. Also see "Will Anti-TIGITs Prove Their Value in 2023?" - In Vivo, 14 December, 2022
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