Topoisomerase II alpha as a universal tumor antigen: antitumor immunity in murine tumor models and H-2K(b)-restricted T cell epitope

Cancer Immunol Immunother. 2010 May;59(5):747-57. doi: 10.1007/s00262-009-0795-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology*
  • Blotting, Western
  • Cancer Vaccines / immunology*
  • DNA Topoisomerases, Type II / immunology*
  • DNA-Binding Proteins / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation
  • Disease Models, Animal
  • Electroporation
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • H-2 Antigens / immunology*
  • Immunotherapy / methods
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / therapy
  • T-Lymphocyte Subsets

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • DNA-Binding Proteins
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • H-2Kb protein, mouse
  • DNA Topoisomerases, Type II