Topoisomerase II alpha as a universal tumor antigen: antitumor immunity in murine tumor models and H-2Kb-restricted T cell epitope
- 259 Downloads
Topoisomerase II alpha (Top2α) 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 Top2α, using dendritic cells (DC) electroporated with RNA encoding the Top2α C-terminus (Top2αCRNA/DC). Top2αCRNA/DC were able to demonstrate in vitro stimulation of T cells from mice that were previously vaccinated with Top2α-expressing tumor lysate-pulsed DC. Vaccination with Top2αCRNA/DC induced Top2α-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-2Kb, also induced Top2α-specific immune responses and antitumor effects. Based on these data, Top2α is suggested to be a universal target for cancer immunotherapy.
KeywordsTopoisomerase II alpha RNA electroporation Dendritic cell Vaccine Tumor antigen
This study was supported by a grant from the Korea Research Foundation (Grant KRF 2006-005-J00602).
- 3.Al-Kuraya K, Novotny H, Bavi P, Siraj AK, Uddin S, Ezzat A, Sanea NA, Al-Dayel F, Al-Mana H, Sheikh SS, Mirlacher M, Tapia C, Simon R, Sauter G, Terracciano L, Tornillo L (2007) HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer. J Clin Pathol 60:768–772CrossRefPubMedGoogle Scholar
- 16.Kanta SY, Yamane T, Dobashi Y, Mitsui F, Kono K, Ooi A (2006) Topoisomerase II alpha gene amplification in gastric carcinomas: correlation with the HER2 gene. An immunohistochemical, immunoblotting, and multicolor fluorescence in situ hybridization study. Hum Pathol 37:1333–1343CrossRefPubMedGoogle Scholar
- 30.Van Tendeloo VF, Ponsaerts P, Lardon F, Nijs G, Lenjou M, Van Broeckhoven C, Van Bockstaele DR, Berneman ZN (2001) Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells. Blood 98:49–56CrossRefPubMedGoogle Scholar
- 34.Wong N, Yeo W, Wong WL, Wong NL, Chan KY, Mo FK, Koh J, Chan SL, Chan AT, Lai PB, Ching AK, Tong JH, Ng HK, Johnson PJ, To KF (2009) TOP2A overexpression in hepatocellular carcinoma correlates with early age onset, shorter patients survival and chemoresistance. Int J Cancer 124:644–652CrossRefPubMedGoogle Scholar