Multifaceted glycoadjuvant@AuNPs inhibits tumor metastasis through promoting T cell activation and remodeling tumor microenvironment

Background: Cytosine-phosphate-guanine (CpG) dinucleotides has been used as adjuvants for cancer immunotherapy. However, unmodified CpG are not very efficient in clinical trials. Glucose, ligand of C-type lectin receptors (CLRs), can promote DC maturation and antigen presentation, which is the first step of induction of adaptive immune responses. Therefore, conjugation of type B CpG DNA to glucose-containing glycopolymers may enhance the therapeutic effects against tumor by CpG-based vaccine. Methods: gCpG was developed by chemical conjugation of type B CpG DNA to glucose-containing glycopolymers. The therapeutic effects of gCpG-based vaccine were tested in both murine primary melanoma model and its metastasis model. Results: gCpG based tumor vaccine inhibited both primary and metastasis of melanoma in mice which was dependent on CD8 + T cells and IFN gamma. In tumor microenvironment, gCpG treatment increased Th1 and CTL infiltration, increased M1 macrophages, decreased Tregs and MDSCs populations, and promoted inflammatory milieu with enhanced secretion of IFN gamma and TNF alpha. The anti-tumor efficacy of gCpG was dramatically enhanced when combined with anti-PD1 immunotherapy. Conclusions: We confirmed that gCpG was a promising adjuvant for vaccine formulation by activating both tumor-specific Th1 and Tc1 responses, and regulating tumor microenvironments.

Automated summary

Chemical conjugation of CpG DNA to glucose-containing glycopolymers can enhance the therapeutic effects of CpG-based vaccines against tumors. The vaccine was found to inhibit both primary and metastatic melanoma in mice, dependent on CD8 + T cells and IFN gamma. Furthermore, in the tumor microenvironment, treatment with gCpG led to increased Th1 and CTL infiltration, increased M1 macrophages, decreased Tregs and MDSCs populations, and promoted an inflammatory milieu with enhanced secretion of IFN gamma and TNF alpha. The anti-tumor efficacy of gCpG was significantly enhanced when combined with anti-PD1 immunotherapy.