Cancer prevention with semi-allogeneic ES cell-derived dendritic cells.
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.
Fukuma
Daiki
D
Department of Immunogenetics, Kumamoto University, Graduate School of Medical Sciences, Kumamoto, Japan.
Matsuyoshi
Hidetake
H
Hirata
Shinya
S
Kurisaki
Akari
A
Motomura
Yutaka
Y
Yoshitake
Yoshihiro
Y
Shinohara
Masanori
M
Nishimura
Yasuharu
Y
Senju
Satoru
S
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D007167:Immunotherapy; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
D000941:Antigens; D008565:Membrane Proteins; D015843:Serpins; D010047:Ovalbumin; D012697:Serine Endopeptidases; C106610:Serpinb9 protein, mouse