Active treatment of murine tumors with a highly attenuated vaccinia virus expressing the tumor associated antigen 5T4 (TroVax) is CD4+ T cell dependent and antibody mediated

Cancer Immunol Immunother. 2006 Sep;55(9):1081-90. doi: 10.1007/s00262-005-0096-4. Epub 2005 Nov 26.

Abstract

5T4 is a tumor associated antigen that is expressed on the surface of a wide spectrum of human adenocarcinomas. The highly attenuated virus, modified vaccinia Ankara, has been engineered to express human 5T4 (h5T4). In a pre-clinical murine model, the recombinant virus (TroVax) induces protection against challenge with CT26-h5T4 (a syngeneic tumor line expressing h5T4). Anti-tumor activity is long lived, with protection still evident 6 months after the final vaccination. In a therapeutic setting, injection of mice with TroVax results in a reduction in tumor burden of >90%. Depletion of CD8+ T cells has no effect upon therapy in the active treatment model, whereas depletion of CD4+ T cells completely abrogates anti-tumor activity. In a prophylactic setting, depletion of CD4+ and CD8+ T cells after the induction of a h5T4 immune response has no deleterious effect on protection following challenge with CT26-h5T4. In light of these studies, the role of antibodies in protection against tumor challenge was investigated. 5T4 specific polyclonal serum decreased tumor burden by approximately 70%. Thus, we conclude that CD4+ T cells are essential for the induction of a protective immune response and that antibodies are the likely effector moiety in this xenogeneic murine tumor model.

MeSH terms

  • Animals
  • Antibodies / metabolism
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antigens, Surface / biosynthesis
  • Antigens, Surface / genetics
  • Antigens, Surface / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / pharmacology
  • Carcinoma / immunology
  • Carcinoma / therapy*
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / therapy*
  • Disease Models, Animal
  • Female
  • Humans
  • Immunotherapy, Active
  • Infusions, Parenteral
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Vaccinia virus / genetics*
  • Vaccinia virus / immunology

Substances

  • Antibodies
  • Antigens, Neoplasm
  • Antigens, Surface
  • Cancer Vaccines
  • Membrane Glycoproteins
  • Recombinant Proteins
  • Tpbg protein, mouse
  • TroVax