Materials and methods for immunosuppressive tumor microenvironment-targeted cancer therapy

Abstract

Many tumors induce and maintain an immunosuppressive tumor microenvironment (TME) that enables tumor to escape host immune system. The present disclosure identifies that cancer cells secrete exosome/microparticle-free, soluble, phosphorylated Hsp70 (pHsp70) (Heat Shock Protein 70 (Hsp70))), which triggers macrophage (M) M2 polarization. It is a further aspect that lipid nanovesicles (NVs) made of dioleoylphosphatidylglycerol (DOPG) and of DOPG complexed with saposin C (SapC) bind to cancer secreted Hsp70, inhibit M differentiation and polarization, and reduce tumor growth. In addition, administration of DOPG-NVs rendered monocytes insensitive to TLR2 (Toll Like Receptor 2) and TLR6 (Toll Like Receptor 6) ligands, suggesting that administration of DOPG-NVs interferes with TLR function.

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