Transcutaneous Tumor Vaccination Combined With aPD-1 Treatment Produces a Synergistic Antitumor Effect

Abstract

Transcutaneous immunization (TCI) has the advantages of safety, high efficiency, non-invasiveness and convenient use. The basis for the realization of TCI is that skin tissue is rich in dendritic cells (DCs) which are the most powerful antigen presenting cells. DCs also play a key role in tumor immunotherapy, which provides a huge imagination for the application of TCI to tumor treatment. In this study, a novel transdermal tumor vaccine (TTV) delivery system was developed based on the electrospun silkfibroin-polyvinyl alcohol (SF-PVA) nanofibrous patch loaded with surface modified ethosome (Eth). Mannosylated PEI (PEI^man) was used to modify Eth, giving the new carrier (termed Eth-PEI^man) the ability to simultaneously load polypeptide antigens and oligonucleotide adjuvants and transdermal targeted DCs delivery. With TRP2 peptide as antigen (encapsulated in Eths) and oligodeoxynucleotides containing unmethylated CpG motifs (absorbed in PEI^man) as adjuvant, the TTV-loaded patches (TTVP) significantly inhibited the growth of melanoma in mouse model. Moreover, the combined application of the TTVP and anti-programmed death-1 monoclonal antibody (aPD-1) produced a synergistic anti-tumor effect, resulting in a much stronger anti-tumor effect, which may be due to the infiltration of more CD4+ and CD8+ T cells in the tumor tissues. The application of TTVP also increased the expression of IL-12, which may be part of the mechanism of synergistic anti-tumor effect between the TTVP and aPD-1. These results suggest that the combination of the TTVP and immune checkpoint blockers could be an effective strategy for tumor treatment. Our work provides a noninvasive and convenient way for improving the efficacy of immune checkpoint blocking therapy as well as prevention of some family hereditary malignancies.

Keywords: transcutaneous immunization; dendritic cells; anti-programmed death-1 monoclonal antibody; ethosome；anti-tumor