Modulating expression of inhibitory and stimulatory immune ‘checkpoints’ using nanoparticulate-assisted nucleic acid delivery

Abstract

Immune checkpoints are regulatory molecules responsible for determining the magnitude and nature of the immune response. The aim of immune checkpoint targeting immunotherapy is to manipulate these interactions, engaging the immune system in treatment of cancer. Clinically, the use of monoclonal antibodies to block immunosuppressive interactions has proven itself to be a highly effective immunotherapeutic intervention. Within the literature there are numerous candidates for next generation of immune checkpoint targeting strategies. One such example is the use of nucleic acid to alter expression levels of immune checkpoint molecules, either as antisense oligo nucleotides/siRNA, to downregulate inhibitory molecules, or mRNA/DNA, to express co-stimulatory molecules. A significant component of nucleic acid delivery is its formulation within a nanoparticulate system. In this review we discuss the progress of the preclinical application of nucleic acid-based immunotherapies to target a selection of co-inhibitory/co-stimulatory molecules. Furthermore, we identify the potential and current gaps within the literature which may form the basis of future work.