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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.

Original publication

DOI

10.1007/s00262-005-0096-4

Type

Journal article

Journal

Cancer Immunol Immunother

Publication Date

09/2006

Volume

55

Pages

1081 - 1090

Keywords

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