Bacterial and cancerous cell membrane fused liposome coordinates with PD-L1 inhibitor for cancer immunotherapy

Abstract

Although tumor cell membranes with broad-spectrum antigens have been explored for cancer vaccines for decades, their relatively poor capacity to stimulate immune responses, especially cellular immune responses, has limited their application. Here, we presented a novel bacterial and cancerous cell membrane fusogenic liposome for co-delivering cell membrane-derived antigens and adjuvants. Meanwhile, a programmed death-ligand 1 (PD-L1) inhibitor, JQ-1, was incorporated into the formulation to tackle the up-regulated PD-L1 expression of antigen-presenting cells (APCs) upon vaccination, thereby augmenting its antitumor efficacy. The fusogenic liposomes demonstrated significantly improved cellular uptake by APCs and effectively suppressed PD-L1 expression in bone marrow-derived dendritic cells (BMDCs) in vitro. Following subcutaneous vaccination, the nanovaccines efficiently drained to the tumor-draining lymph nodes (TDLNs), and significantly inhibited PD-L1 expression of both dendritic cells (DCs) and macrophages within the TDLNs and tumors. As a result, the liposomal vaccine induced robust innate and cellular immune responses and inhibited tumor growth in a colorectal carcinoma-burden mouse model. In summary, the fabricated cell membrane-based fusogenic liposomes offer a safe, effective, and easily applicable strategy for tumor immunotherapy and hold potential for personalized cancer immunotherapy.