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

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 ag...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2006-09, Vol.55 (9), p.1081-1090
Main Authors: HARROP, Richard, RYAN, Matthew G, MYERS, Kevin A, REDCHENKO, Irina, KINGSMAN, Susan M, CARROLL, Miles W
Format: Article
Language:English
Subjects:
Animal models
Animals
Antibodies
Antibodies - metabolism
Antigens
Antigens, Neoplasm - biosynthesis
Antigens, Neoplasm - genetics
Antigens, Neoplasm - immunology
Antigens, Surface - biosynthesis
Antigens, Surface - genetics
Antigens, Surface - immunology
Antineoplastic agents
Antitumor agents
Biological and medical sciences
Cancer
Cancer Vaccines - genetics
Cancer Vaccines - immunology
Cancer Vaccines - pharmacology
Carcinoma - immunology
Carcinoma - therapy
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cloning
Colonic Neoplasms - immunology
Colonic Neoplasms - therapy
Disease Models, Animal
Female
Humans
Immunotherapy
Immunotherapy, Active
Infusions, Parenteral
Lymphocytes
Lymphocytes T
Medical sciences
Membrane Glycoproteins
Metastasis
Mice
Mice, Inbred BALB C
Original
Pharmacology. Drug treatments
Recombinant Proteins - metabolism
Recombinant Proteins - pharmacology
Tumors
Vaccination
Vaccines
Vaccines, DNA
Vaccinia virus - genetics
Vaccinia virus - immunology
Viruses
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Items that cite this one
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Summary: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.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-005-0096-4