Targeting Immune Checkpoints with Therapeutic Monoclonal Antibodies: Mechanisms and Therapeutic Advances

Abstract

Targeting immune checkpoints including PD-1, PD-L1, and CTLA-4 with monoclonal antibodies have transformed cancer immunotherapy by altering T-cell signaling pathway. This review examines the molecular mechanisms underlying immune checkpoint blockade and discusses the current landscape of FDA-approved therapies, ongoing clinical trials, and next-generation checkpoint targets. Emphasis is placed on resistance mechanisms, biomarker development for patient selection, and combinatorial strategies to overcome therapeutic limitations.  Furthermore, this study explores the potential of antibody engineering in future such as bispecific antibodies and Fc optimization. Merging the mechanistic insights with advancements in clinical and future thinking, we address the issue of personalized medicinal approach, and immune related adverse reaction.