Bacterial and cancerous cell membrane fused liposome coordinates with PD-L1 inhibitor for cancer immunotherapy
Xianjin Luo, Chenglong Li, Zhaofei Guo, Hairui Wang, Penghui He, Yuanhao Zhao, Yi Lin, Chun‐Ting He, Yingying Hou, Yongshun Zhang, Guangsheng Du
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.