Massive parallel screening of phage libraries for the generation of repertoires of human immunomodulatory monoclonal antibodies.

Immune checkpoints are emerging as novel targets for cancer therapy, and antibodies against them have shown remarkable clinical efficacy with potential for combination treatments to achieve high therapeutic index. This work aims at providing a novel approach for the generation of several novel human immunomodulatory antibodies capable of binding their targets in their native conformation and useful for therapeutic applications. We performed a massive parallel screening of phage libraries by using for the first time activated human lymphocytes to generate large collections of single-chain variable fragments (scFvs) against 10 different immune checkpoints: LAG-3, PD-L1, PD-1, TIM3, BTLA, TIGIT, OX40, 4-1BB, CD27 and ICOS.