Cancer prevention with semi-allogeneic ES cell-derived dendritic cells.
Biochemical and biophysical research communications 2005 Sep 16; 335(1):5-13
Fukuma D D, Matsuyoshi H H, Hirata S S, Kurisaki A A, Motomura Y Y, Yoshitake Y Y, Shinohara M M, Nishimura Y Y, Senju S S
Department of Immunogenetics, Kumamoto University, Graduate School of Medical Sciences, Kumamoto, Japan.
Dendritic cells (DC) genetically modified to present tumor-associated antigen are a promising means for anti-cancer immunotherapy. By introducing expression vectors into ES cells and subsequently inducing differentiation to DC (ES-DC), we can generate transfectant DC expressing the transgenes. In the future clinical application of this technology, the unavailability of human ES cells genetically identical to the patients will be a problem. However, in most cases, semi-allogeneic ES cells sharing some of HLA alleles with recipients are expected to be available. In the present study, we observed that model tumor antigen (OVA)-expressing mouse ES-DC transferred into semi-allogeneic mice potently primed OVA-reactive CTL and elicited a significant protection against challenge with OVA-expressing tumor. Genetic modification of ES-DC to overexpress SPI-6, the specific inhibitor of granzyme B, further enhanced their capacity to prime antigen-specific CTL in semi-allogeneic recipient mice. These results suggest the potential of ES-DC as a novel means for anti-cancer immunotherapy.