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 S Au 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.

中文翻译：

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基于光热消融的疫苗与免疫检查点阻断相结合用于协同骨肉瘤免疫治疗

摘要 骨肉瘤是一种严重威胁人类健康的骨恶性肿瘤，而常规化疗药物治疗效果不佳且副作用严重。在这里，通过将基于光热消融的原位肿瘤疫苗与 PD-1/PD-L1 阻断免疫疗法相结合，开发了一种针对原发性和转移性肿瘤的多方法。聚乙烯亚胺修饰的金纳米棒 (GNR-PEI) 是通过超支化 PEI 通过 S Au 键与 GNR 共轭而制备的。带正电荷的 GNR-PEI 可以通过静电相互作用与环状二聚鸟苷单磷酸-腺苷单磷酸 (cGAMP) 复合。GNR-PEI/cGAMP 复合物进一步用于原发性肿瘤的近红外激光触发光疗，生成原位肿瘤疫苗，招募树突状细胞 (DC) 以捕获肿瘤相关抗原。此外，cGAMP是一种干扰素基因刺激剂（STING）激动剂，可以刺激DCs的扩增和活化，引起细胞毒性T细胞的特异性免疫杀伤作用。此外，局部肿瘤疫苗与程序性细胞死亡蛋白-1（PD-1）单克隆抗体（抗PD-1）的结合，可实现检查点阻断和逆转肿瘤免疫耐受微环境，从而提高T细胞特异性识别并杀死剩余和转移的肿瘤细胞。因此，这种联合策略有望进一步用于骨肉瘤的临床治疗。局部肿瘤疫苗与程序性细胞死亡蛋白-1（PD-1）单克隆抗体（抗PD-1）相结合，可实现检查点阻断和逆转肿瘤免疫耐受微环境，从而提高T细胞特异性识别和杀伤残留和转移的肿瘤细胞。因此，这种联合策略有望进一步用于骨肉瘤的临床治疗。局部肿瘤疫苗与程序性细胞死亡蛋白-1（PD-1）单克隆抗体（抗PD-1）相结合，可实现检查点阻断和逆转肿瘤免疫耐受微环境，从而提高T细胞特异性识别和杀伤残留和转移的肿瘤细胞。因此，这种联合策略有望进一步用于骨肉瘤的临床治疗。