Topoisomerase II alpha as a universal tumor antigen: antitumor immunity in murine tumor models and H-2K(b)-restricted T cell epitope.
Topoisomerase II alpha (Top2alpha) is an attractive candidate to be used as a tumor antigen for cancer immunotherapy, because it is abundantly expressed in various tumors and serves as a target for a number of chemotherapeutic agents. In this study, we demonstrated the immunogenicity of Top2alpha, using dendritic cells (DC) electroporated with RNA encoding the Top2alpha C-terminus (Top2alphaCRNA/DC). Top2alphaCRNA/DC were able to demonstrate in vitro stimulation of T cells from mice that were previously vaccinated with Top2alpha-expressing tumor lysate-pulsed DC. Vaccination with Top2alphaCRNA/DC induced Top2alpha-specific T cell responses in vivo as well as antitumor effects in various murine tumor models including MC-38, B16F10, and GL26. DC pulsed with p1327 (DSDEDFSGL), defined as an epitope presented by H-2K(b), also induced Top2alpha-specific immune responses and antitumor effects. Based on these data, Top2alpha is suggested to be a universal target for cancer immunotherapy.
Park
Jung-Sun
JS
Department of Microbiology and Immunology, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul, Korea.
Kim
Hye-Sung
HS
Park
Mi-Young
MY
Kim
Chang-Hyun
CH
Chung
Yeun-Jun
YJ
Hong
Yong-Kil
YK
Kim
Tai-Gyu
TG
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000276:immunology*; D004250:DNA Topoisomerases, Type II / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D004195:Disease Models, Animal; D018274:Electroporation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D016176:T-Lymphocyte Subsets
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D004250:DNA Topoisomerases, Type II