Combination of GNRs-PEI/cGAMP-laden macrophages-based photothermal induced in situ tumor vaccines and immune checkpoint blockade for synergistic anti-tumor immunotherapy

Abstract

Immunotherapy is an effective strategy to control and eliminate primary and metastatic tumor by restarting and restoring the specific anti-tumor immune response. However, tumor immunotherapy often showed limited efficacy due to the poor T cell responses in vivo and the tumor suppressive microenvironments. Herein, we constructed polyethyleimine modified gold nanorods (GNRs-PEI) by conjugating PEI to GNRs via SAu bonds. GNRs-PEI/cGAMP nanoparticles were formed via electrostatic interaction and then loaded by macrophages. The GNRs-PEI/cGAMP-laden macrophages (GPc-RAWs) were intravenously injected into the tumor bearing mice and the in situ tumor vaccines were obtained after NIR irradiation. Besides, anti-PD-L1 antibody, an immune checkpoint inhibitor, was introduced to reverse immunosuppressive microenvironment and assisted to achieve the synergistic anti-tumor immunotherapy. GNRs-PEI/cGAMP-laden macrophages with NIR irradiation could effectively inhibit the primary tumors, while little effect for the contralateral tumors. When combined with anti-PD-L1 antibody, the combined strategy not only inhibited the growth of primary tumor, but also significantly delayed the proliferation of the contralateral tumors. More importantly, this strategy reversed immunosuppressive microenvironment without obvious side effects. Therefore, this study provided a great immunotherapy platform for the efficient treatment of primary and metastatic tumors.

Keywords: Immune checkpoint blockade; Immunotherapy; Macrophages mediated strategy; Photothermal therapy; Synergistic treatment.