(117a) Transdermal Cancer Vaccine Using Antigen-Coating Nano Drug Carrier

Transcutaneous
immunization using the skin's immune system is increasingly attracting attention.
In contrast to conventional immunization by injection, transcutaneous
immunization requires only topical application of antigens to the skin and is a
simple, non-invasive immunization method that does not require medical
personnel. Furthermore, the epidermal and dermal layers of skin contain an abundance
of antigen-presenting cells (APCs) such as Langerhans cells (LCs) and dermal
dendritic cells (dDCs). These APCs capture antigens,
migrate to the lymph node from the skin, and then induce antigen-specific
immunity by antigen presentation. Using the skin's immune system,
transcutaneous immunization can offer a more effective method than subcutaneous
(s.c.) or intramuscular injection. However, the major
problem in transcutaneous administration is that the stratum corneum (SC), the outermost layer of the skin, serves as a
hydrophobic barrier at the skin surface that hinders the penetration of
hydrophilic biomolecules (M_w > 500 Da). Because most antigens are
hydrophilic molecules, such as proteins and peptides, it is difficult to
deliver antigens to APCs through the skin.

To overcome
the SC barrier and induce immunity by topical application of antigens, various
antigen formulations have been developed, including hydrogel patches, poly(lactic acid) nanoparticles, chitosan nanoparticles, and
flexible liposomes. Our approach is to coat the hydrophilic antigens with
hydrophobic surfactant molecules using water-in-oil (W/O) emulsification,
followed by freeze-drying to produce oil-dispersible antigen–surfactant
complexes. Because hydrophobic materials are more permeable through the
hydrophobic SC than hydrophilic materials, oil dispersions of the complexes,
namely solid-in-oil (S/O) nanodispersions, can
improve the delivery of antigens into the skin. Using the S/O technique, we
previously demonstrated antigen-specific antibody production by transcutaneous
immunization, without physical enhancement or pre-treatment of skin. Furthermore,
co-encapsulation of polyarginine as a skin
penetration enhancer or CpG oligodeoxynucleotide
as an immune adjuvant in S/O nanodispersions induced
antibody production more effectively.

In this study, we applied the S/O nanodispersion technique to the induction of cancer
immunity by transdermal delivery of cancer antigen. Cancer immunotherapy by
activation of immune system against cancer has recently received attention for its
feasibility in the treatment of malignancies with little toxicity. The key step
for inducing the cancer immunity is the delivery of cancer-specific antigens to
DCs, followed by the antigen-presenting by the DCs. We
prepared S/O nanodispersions bearing ovalbumin (OVA)
as a model cancer-antigen for efficient transdermal OVA delivery. Our investigation
revealed the ability of this approach to induce antigen-specific cellular
immune responses against cancer by evaluating the growth of OVA-bearing tumors
and the production of cytokines from splenocytes. Inhibition of OVA-bearing tumor growth was achieved,
demonstrating the applicability of S/O nano carriers
to the induction of cancer immunity.