Liver specific gene immunotherapies resolve immune suppressive ectopic lymphoid structures of liver metastases and prolong survival.

ABSTRACT: The ability to generate potent immunotherapies locally and transiently for the treatment of cancers is a promising strategy to improve efficacy and decrease off-target toxicities. Here, we explored an alternative approach for the delivery of immunotherapeutic agents, in which we deliver the pDNA of an engineered PD-L1 trap and/or CXCL12 trap to the nucleus of liver hepatocytes via a lipid calcium phosphate nanoparticle. This strategy greatly increased the concentrations of immunotherapeutic agents in the local tissue, allowing the therapy to inhibit the accumulation of immune suppressive cells and liver metastasis. Furthermore, we find that the lipid calcium phosphate nanoparticles containing the pCXCL12 trap resolved the formation of immune suppressive ectopic lymphoid structures, while t

SUBMITTER: Goodwin TJ 

PROVIDER: S-EPMC5557391 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature