Hydrogel/nanoadjuvant-mediated combined cell vaccines for cancer immunotherapy.

Combined cell vaccines of tumor whole cells and dendritic cells (DCs) provide an effective individualized immunotherapy for malignant tumors. We propose an innovative strategy termed "biomaterial-mediated combined cell vaccines for immunotherapy," which combines tumor cell and DC vaccines with a cyclodextrin-polyethylene glycol hydrogel and a cytosine-phosphate-guanine (CpG) nanoadjuvant. The nanoadjuvant promotes antigen presentation and amplifies immune-eliciting potency by co-delivery of antigens and adjuvants. The hydrogel scaffold provides a better growth microenvironment for injected exogenous DCs and recruits endogenous DCs to maintain their viability for synergistic effect. The results indicated that, relative to live tumor cells, the immunogenically dying tumor cells activated DC maturation effectively with the auxiliary effect of immune adjuvant CpG nanoparticles. The increased T cell percentage, proliferation ability, cytokine secretion, and cytotoxic effect revealed the enhanced immunogenicity of the combined cell vaccines. The combined hydrogel/nanoadjuvant system showed the best efficiency in inhibiting tumor growth. Moreover, vaccination with a single dose of hydrogel-based combined vaccines significantly delayed the development of tumors. The biomaterial-mediated combined cell vaccines remarkably increased the infiltration of effector T cells, alleviated the intratumoral immunosuppressive microenvironment, and maximized the immune effect of the vaccines, thus improving cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Cell-based vaccines, including tumor whole-cell vaccine or DC vaccine, have attracted wide attention as an effective method for cancer immunotherapy. However, it is difficult to gain satisfactory outcomes in clinical trials because of the low immunogenicity of tumor whole cell vaccine and the short-term survival of transferred DC vaccine. Therefore, improving the ability of cell-based vaccines to induce a strong and durable immune response is the primary objective for vaccine development. Biomaterial-mediated combined cell vaccines is an innovative strategy for cancer immunotherapy. The combined hydrogel/ nanoadjuvant system comprises immunogenically dying tumor cells, DCs, and nanoadjuvants. Nanoadjuvant-loaded immunogenically dying tumor cells can induce efficient immune response as the tumor cell vaccine. The hydrogel-based combined tumor cell/DC vaccine could be used for individualized immunotherapy.