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

• Published in: Cancer Immunology, Immunotherapy Vol. 55; no. 9; pp. 1081 - 1090
• Main Authors: HARROP, Richard, RYAN, Matthew G, MYERS, Kevin A, REDCHENKO, Irina, KINGSMAN, Susan M, CARROLL, Miles W
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.09.2006; Springer Nature B.V; Springer-Verlag
• 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; United Kingdom > UK; Ankara Turkey; Turkey; T lymphocytes; Chordopoxvirinae; Immune response; Tumor immunity; Tumor associated antigen; Antibody; Orthopoxvirus; Rodentia; Antibodies; Helper cell; Malignant tumor; Gene expression; Virus; Vaccinia virus; Vertebrata; Mammalia; Treatment; Mouse; Poxviridae; Animal; Immunotherapy; T-Lymphocyte; Rodent
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-005-0096-4

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.