MRNA Vaccine with Antigen-Specific Checkpoint Blockade Induces an Enhanced Immune Response against Established Melanoma.

ABSTRACT: We reported a preclinical cancer vaccine that simultaneously introduced an mRNA antigen and an immune checkpoint blocking siRNA into the antigen-presenting cells. This was achieved by formulating both nucleic acid-based immunotherapeutics into a lipid-coated calcium phosphate (LCP) nanoparticle (NP) as a carrier to address the delivery challenge. The PEGylated lipid NPs were functionalized with mannose as the targeting ligand to facilitate the preferential uptake by the dendritic cells (DCs) in the lymph nodes after subcutaneous administration. The calcium phosphate core allowed acid-mediated dissolution in the endo-lysosomal compartment, which prompted rapid release of cargoes after cellular internalization of NP. LCP mRNA vaccine encoding TRP2 elicited a robust antigen-specific cytotoxic

SUBMITTER: Wang Y 

PROVIDER: S-EPMC5835019 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature