Nucleic acid-based immune checkpoint blockade: Progress and potential

Abstract Engaging the immune system through checkpoint blockade has become a standard of care in the treatment of many tumors. Traditionally, immune checkpoint blockade involves the use of monoclonal antibodies and whilst these have been extremely successful clinically, there is significant scope for improvement. The use of nucleic acid offers a potential alternative to monoclonal antibodies as it can both silence and express immunosuppressive and immunostimulatory molecules. This chapter seeks to outline the exciting progress and future potential of nucleic acid based immune checkpoint blockade. Specifically, it will review the preclinical work performed using siRNA, mRNA, or pDNA with a focus on summarizing the findings of nucleic acid–based checkpoint blockade for each target.