(690g) Nanoscale Approaches for Targeting Tumor-Associated Macrophages (INVITED SPEAKER)

Tumors are heavily infiltrated with tumor-associated macrophages (TAM), which facilitate tumor progression and, directly and indirectly mount an immune suppressive effect on T cells. TAMs are polarized to M2-like phenotype which are known to promote tumor growth. In contrast, M1 macrophages possess enhanced cytotoxic activity, produce inflammatory cytokines, and have antigen presenting capability. Here, we show that an effective strategy to repolarize the M2 TAMs to M1 phenotype could be devised by tumor-specific inhibition of Colony-stimulating factor-1 (CSF-1) signaling in M2 TAMs. To achieve this, we have developed a completely new platform technology, called supramolecular nanotherapeutics (SNTs) where we designed a CSF-1R inhibiting molecular subunit that can self-assemble with each other and with additional inactive excipients to form nanoscale structures. We have shown that SNTs enabled significant re-polarization of M2 macrophages to M1 phenotype and enhanced phagocytosis of cancer cells. We have also shown that these CSF-1R inhibiting supramolecular nanotherapeutics significantly enhance anti-cancer efficacy without any significant toxicity. This study shows that a successful strategy to overcome immune suppression and improve cancer immunotherapy could be devised by a CSF-1R inhibiting supramolecular nanotherapeutics that can alter the innate immune contexture of tumors by switching the immunosuppressive M2 macrophages to effector M1 macrophages.