Nanoparticle-Mediated In Situ Molecular Reprogramming of Immune Checkpoint Interactions for Cancer Immunotherapy

resulting in 75% knockdown of inhibitory checkpoint (PDL1) expression and simultaneously express high levels of stimulatory checkpoint (OX40L) with minimal toxicity. Intratumoral treatment with the proposed formulation resulted in statistically reduced tumor growth, a greater density of CD4+ and CD8+ infiltrates in the tumor, and immune activation within tumor-draining lymph nodes. These data suggest that a single RNA-based formulation can successfully reprogram multiple immune checkpoint interactions on a cellular level. Such a candidate may be able to replace future immune checkpoint therapeutic regimes composed of both stimulatory- and inhibitory-receptor-targeting antibodies.