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.

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.

• Authors: Richard Harrop, Matthew G Ryan, Kevin A Myers, Irina Redchenko, Susan M Kingsman, Miles W Carroll
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 55 Issue 9 Pg. 1081-90 (Sep 2006) ISSN: 0340-7004 [Print] Germany
• PMID: 16311730 (Publication Type: Journal Article)

Chemical References

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

Topics

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