ab9b00260_si_001.pdf (4.46 MB)
Transcutaneous Codelivery of Tumor Antigen and Resiquimod in Solid-in-Oil Nanodispersions Promotes Antitumor Immunity
Version 2 2019-04-30, 11:03
Version 1 2019-04-26, 16:07
journal contribution
posted on 2019-04-18, 00:00 authored by Rie Wakabayashi, Hidetoshi Kono, Shuto Kozaka, Yoshiro Tahara, Noriho Kamiya, Masahiro GotoCancer vaccines aim
to prevent or inhibit tumor growth by inducing
an immune response to tumor-associated antigens (TAAs) encoded by
or present in the vaccine. Previous work has demonstrated that effective
antitumor immunity can be induced using a codelivery system in which
nonspecific immunostimulatory molecules are administered together
with TAAs. In this study, we investigated the antitumor effects of
a solid-in-oil (S/O) nanodispersion system containing a model TAA,
ovalbumin (OVA), and resiquimod (R-848), a small molecular Toll-like
receptor 7/8 ligand, which induces an antigen-nonspecific cellular
immune response that is crucial for the efficacy of cancer vaccines.
R-848 was contained in the outer oil phase of S/O nanodispersion.
Analysis of OVA and R-848 permeation in mouse skin after application
of an R-848 S/O nanodispersion indicated that R-848 rapidly permeated
the skin and preactivated Langerhans cells, resulting in efficient
uptake of OVA and migration of antigen-loaded Langerhans cells to
the draining lymph nodes. Transcutaneous immunization of mice with
an R-848 S/O nanodispersion inhibited the growth of E.G7-OVA tumors
and prolonged mouse survival to a greater extent than did immunization
with an S/O nanodispersion containing OVA alone. Consistent with this
observation, antigen-specific secretion of the Th1 cytokine interferon-γ
and cytolytic activity were both high in splenocytes isolated from
mice immunized with R-848 S/O. Our results thus demonstrate that codelivery
of R-848 significantly amplified the antitumor immune response induced
by antigen-containing S/O nanodispersions and further suggest that
S/O nanodispersions may be effective formulations for codelivery of
TAAs and R-848 in transcutaneous cancer vaccines.