Combining photothermal ablation-based vaccine with immune checkpoint blockade for synergistic osteosarcoma immunotherapy. (15th January 2021)

• Record Type: Journal Article
• Authors: Zhao, Xingyu; Han, Yu; Sun, Yang; Feng, Wei; Liu, Jianguo; Li, Dongsong; Wang, Tiejun
• Is Part Of: Materials & design. Volume 198(2021)
• Publication Date: 2021-01-15
• Subjects: Tumor vaccine -- Immune checkpoint blockade -- Osteosarcoma -- Photothermal therapy -- Metastasis; Materials -- Periodicals; Engineering design -- Periodicals; Matériaux -- Périodiques; Conception technique -- Périodiques; Electronic journals; 620.11
• DOI: 10.1016/j.matdes.2020.109311
• Languages: English
• ISSNs: 0264-1275

Abstract

Abstract: Osteosarcoma is a serious bone malignancy that threatens to human health, while the conventional chemotherapy exhibits ineffective and severe side effects. Here, a multi-approach for primary and metastatic tumors was developed by combining photothermal ablation-based in situ tumor vaccine with PD-1/PD-L1 blockade immunotherapy. Polyethyleimine modified golden nanorod (GNR-PEI) was prepared by conjugating of hyperbranched PEI to GNR via SAu bonds. The positive charged GNR-PEI could complex with cyclic dimeric guanosine monophosphate-adenosine monophosphate (cGAMP) by electrostatic interaction. GNR-PEI/cGAMP complex was further utilized for near-infrared laser-triggered phototherapy of primary tumors, generating in situ tumor vaccine, recruiting dendritic cells (DCs) to capture tumor-associated antigens. In addition, cGAMP is a kind of stimulator of interferon genes (STING) agonist that can stimulate the expansion and activation of DCs, arousing the specific immune killing effect of cytotoxic T cells. Furthermore, the combination of localized tumor vaccine and programmed cell death protein-1 (PD-1) monoclonal antibody (anti-PD-1), that could achieve the checkpoint-blockade and reverse tumor immune tolerance microenvironment, thus improving T cells specific recognition and killing of remaining and metastasis tumor cells. Hence, this combined strategy is expected to be further used in the clinical treatment of osteosarcoma. Graphical abstract: Unlabelled Image Highlights: Facilely constructed by simple blending of GNR-PEI with cGAMP via electrostatic interactions. Photothermal induced in situ whole tumor cell associated antigens and adjuvant. Synergistic antitumor effect by tumor vaccine and immune checkpoint blockade.