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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
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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
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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
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Journal Article
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
2006
Overview
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.
Publisher
Springer,Springer Nature B.V,Springer-Verlag
Subject
/ Animals
/ Antigens
/ Antigens, Neoplasm - biosynthesis
/ Antigens, Neoplasm - genetics
/ Antigens, Neoplasm - immunology
/ Antigens, Surface - biosynthesis
/ Antigens, Surface - genetics
/ Antigens, Surface - immunology
/ Biological and medical sciences
/ Cancer
/ Cancer Vaccines - immunology
/ Cancer Vaccines - pharmacology
/ CD4-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - immunology
/ Cloning
/ Colonic Neoplasms - immunology
/ Female
/ Humans
/ Mice
/ Original
/ Pharmacology. Drug treatments
/ Recombinant Proteins - metabolism
/ Recombinant Proteins - pharmacology
/ Tumors
/ Vaccines
/ Viruses
