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
| Autor: | Miles W. Carroll, Kevin Alan Myers, Irina Redchenko, Susan M. Kingsman, Richard Harrop, Matthew G. Ryan |
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| Rok vydání: | 2005 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cancer Research Modified vaccinia Ankara medicine.medical_treatment Immunology Vaccinia virus Biology CD8-Positive T-Lymphocytes Cancer Vaccines Antibodies Mice Immune system Antigen Antigens Neoplasm medicine Vaccines DNA Immunology and Allergy Animals Humans Infusions Parenteral Mice Inbred BALB C TroVax Membrane Glycoproteins Carcinoma Immunotherapy Active Immunotherapy T lymphocyte Recombinant Proteins Disease Models Animal Oncology Antigens Surface Colonic Neoplasms Cancer research biology.protein Female Antibody CD8 |
| Zdroj: | Cancer immunology, immunotherapy : CII. 55(9) |
| ISSN: | 0340-7004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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