Hybrid Membrane Nanovaccines Combined with Immune Checkpoint Blockade to Enhance Cancer Immunotherapy

Peiqi Zhao,1,* Yuanlin Xu,2,* Wei Ji,3 Lanfang Li,1 Lihua Qiu,1 Shiyong Zhou,1 Zhengzi Qian,1 Huilai Zhang1 1Department of Lymphoma, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People’s Republic of China; 2Department of Lymphatic Comprehensive Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 3Public Laboratory, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peiqi Zhao; Huilai ZhangDepartment of Lymphoma, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People’s Republic of ChinaTel +86-22-23340123Email peiqizhao@126.com; zhanghltch@163.comPurpose: Cancer vaccines are a promising therapeutic approach in cancer immunotherapy and can inhibit tumor growth and prevent tumor recurrence and metastasis by activating a sustained antitumor immunoprotective effect. However, the therapeutic effect of cancer vaccines is severely weakened by the low immunogenicity of cancer antigens and the immunosuppressive microenvironment in tumor tissues.Methods: Here, we report a novel hybrid membrane nanovaccine, composed of mesoporous silica nanoparticle as a delivery carrier, hybrid cell membranes obtained from dendritic cells and cancer cells, and R837 as an immune adjuvant (R837@HM-NPs). We investigated the anti-tumor, tumor recurrence and metastasis prevention abilities of R837@HM-NPs and their mechanisms of action through a series of in vivo and ex vivo experiments.Results: R837@HM-NPs not only provide effective antigenic stimulation but are also a durable supply of the immune adjuvant R837. In addition, R837@HM-NPs promote antigen endocytosis into dendritic cells via various receptor-mediated pathways. Compared with HM-NPs or R837@HM-NPs, R837@HM-NPs in combination with an immune checkpoint blockade showed stronger antitumor immune responses in inhibiting tumor growth, thus eliminating established tumors, and rejecting re-challenged tumors by regulating the immunosuppressive microenvironment and immunological memory effect.Conclusion: These findings suggest that the hybrid membrane nanovaccine in combination with immune checkpoint blockade is a powerful strategy to enhance antitumor immunotherapy without concerns of systemic toxicity.Keywords: hybrid membrane, immune checkpoint blockade, immunotherapy, mesoporous silica nanoparticle, nanovaccine