Low response rate of immune checkpoint blockade (ICB) has limited its clinical application. A promising strategy to overcome this limitation is the use of therapeutic cancer vaccines, which aim to induce robust immune responses that synergize with ICB through immune enhancement and immune normalization strategies. Herein, we developed a combination immunotherapy by combining nano-vaccines consisting of whole tumor cell lysates/CpG liposomes (LCLs) with an anti-PD-L1 loaded lipid gel (aPD-L1@LG). The LCLs were fabricated using cationic liposomes, while the lipid gels (LGs) were prepared by using soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO). Subcutaneous administration of LCLs successfully activated dendritic cells (DCs), and intratumoral administration of anti-PD-L1@LG ensured sustained ICB activity. These results demonstrated that this combination immunotherapy enhanced anti-tumor efficacy and prolonged the survival time in melanoma by activating systemic anti-tumor immune responses. These findings highlight the potential of this rational design as a promising strategy for tumor treatment.

免疫检查点阻断（ICB）的低反应率限制了其临床应用。克服这一限制的一个有前途的策略是使用治疗性癌症疫苗，其目的是通过免疫增强和免疫正常化策略诱导与 ICB 协同的强大免疫反应。在此，我们开发了一种联合免疫疗法，将由全肿瘤细胞裂解物/CpG脂质体（LCL）组成的纳米疫苗与负载抗PD-L1的脂质凝胶（aPD-L1@LG）相结合。LCL 使用阳离子脂质体制备，而脂质凝胶 (LG) 使用大豆磷脂酰胆碱 (SPC) 和甘油二油酸酯 (GDO) 制备。皮下注射 LCL 成功激活树突状细胞 (DC)，瘤内注射抗 PD-L1@LG 确保了持续的 ICB 活性。这些结果表明，这种联合免疫疗法通过激活全身抗肿瘤免疫反应，增强了黑色素瘤的抗肿瘤功效并延长了生存时间。这些发现凸显了这种合理设计作为一种有前途的肿瘤治疗策略的潜力。