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Engineering Dendritic-Cell-Based Vaccines and PD‑1 Blockade in Self-Assembled Peptide Nanofibrous Hydrogel to Amplify Antitumor T‑Cell Immunity
journal contribution
posted on 2018-06-22, 00:00 authored by Pengxiang Yang, Huijuan Song, Yibo Qin, Pingsheng Huang, Chuangnian Zhang, Deling Kong, Weiwei WangDendritic
cells (DCs) are increasingly used in cancer vaccines
due to their ability to regulate T-cell immunity. Major limitations
associated with the present DC adoptive transfer immunotherapy are
low cell viability and transient duration of transplanted DCs at the
vaccination site and the lack of recruitment of host DCs, leading
to unsatisfactory T-cell immune response. Here, we developed a novel
vaccine nodule comprising a simple physical mixture of the peptide
nanofibrous hydrogel, anti-PD-1 antibodies, DCs, and tumor antigens.
Upon subcutaneous injection, the vaccine nodule maintained the viability
and biological function including the antigen uptake and maturation
of encapsulated DCs and simultaneously recruited a number of host
DCs and promoted the drainage of activated DCs to lymph nodes, resulting
in enhanced proliferation of antigen-specific splenocytes and provoking
potent cellular immune responses. Compared with adoptive transfer
of DCs and subcutaneous administration of antigen vaccine, such a
vaccine nodule shows superior antitumor immunotherapy efficiency in
both prophylactic and therapeutic tumor models including delayed tumor
growth and prolonged mice survival due to effective stimulation of
antitumor T-cell immunity and increased infiltration of activated
CD8+ effector T-cells in the tumor. Our findings provide
a simple and robust vaccination strategy for DC-based vaccines and
also a unique vaccine product for stimulating and enhancing T-cell
immunity, holding great promise for immunotherapy against cancer and
infectious diseases.