Hydrogel/Nanoadjuvant-Mediated Combined Cell Vaccines for Cancer Immunotherapy

Abstract

Cancer immunotherapy aims to effectively eliminate the residual tumor cells and prevent tumor recurrence and metastasis. The combined cell vaccines of tumor whole cell and dendritic cells (DC) provide an effective individualized immunotherapy for malignant tumors. It is a key issue how to improve the immunogenicity of tumor whole cell vaccine and maintain DC activity for antigen presentation in vivo. We proposed an innovative strategy called “biomaterial-mediated combined cell vaccines for immunotherapy”, which combined tumor cell vaccine and DC vaccine by cyclodextrin-polyethylene glycol hydrogel and CpG nanoadjuvant. The nanoadjuvant promoted antigen presentation level and amplified immune eliciting potency by co-delivery of antigen and adjuvant. The hydrogel scaffold provided a better growth microenvironment for injected exogenous DC and recruited endogenous DC to maintain their viability and play their synergistic action. Based on effective antigen presentation from the combination of tumor antigen, adjuvant and DC, the combined cell vaccines induced strong CTL killing effect to continuously stimulate the body's specific anti-tumor immunity. The combined hydrogel/ nanoadjuvant system merged immunogenically dying tumor cells, DC and adjuvants, which remarkably increased the infiltration of effector T cells, alleviated the intratumoral immunosuppressive microenvironment and maximized the immune effect of the vaccines for improving the cancer immunotherapy.