We then demonstrated that human cells transfected with ovalbumin (OVA) antigen and loaded with α-GalCer could also generate both innate and adaptive immunity in wild-type mice. We also assessed the safety of this approach in a canine large animal model. Physical examination, blood chemistry analysis, and autoantibody tests, as well as tissue biopsies from liver, lung, and other organs from dogs given high-dose aAVCs, confirmed the safety of this method in addition to its efficacy in generating immunologic responses (Shimizu et al. 2013).

A final preclinical study was performed to determine whether tumor antigen-specific T cell responses seen in allogeneic studies could also be generated in an autologous setting. For this purpose, we developed a novel humanized mouse model using NOD/Shi-scid/IL-2Rγc ^null (NOG) mice. T cells from healthy HLA-A2+ donors were transduced with the MART (melanoma antigen recognized by T cells)-1 tumor antigen TCR gene and adoptively transferred into NOG mice. This was followed by intravenous transfer of syngeneic immature DCs and iNKT cells. Finally, aAVCs transduced with MART-1 mRNA and loaded with α-GalCer were transferred into one group of mice but not controls. As expected, the transferred TCR gene-transduced T cells expanded robustly in mice receiving MART-1 expressing aAVC but not controls (Shimizu et al. 2013).

Thus far, our current pre-clinical studies demonstrate the safety and efficacy of aAVCs in harnessing the innate and adaptive immune systems through targeting of in situ DCs. This model system, which uses different arms of the immune system to generate a systemic and specific anti-tumor response, could prove clinically beneficial as immunotherapies against a number of malignant diseases.