A recombinant vaccinia virus containing the papilloma E2 protein promotes tumor regression by stimulating macrophage antibody-dependent cytotoxicity |
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Authors: | Carlos Rosales Viviana Valadez Graham Gerardo Arrellín Rosas Horacio Merchant Ricardo Rosales |
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Institution: | (1) Department of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico, MX;(2) Department of Molecular Biology, Instituto de Investigaciones Biomédicas – UNAM, Apto. Postal 70228, Cd. Universitaria, México, D.F. – 04510, Mexico e-mail: roleri@servidor.unam.mx Tel.: +52-5622-3825 Fax: 52-5550-0048, MX;(3) Department of Cell Biology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico, MX |
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Abstract: | Human papillomavirus infection is associated with cervical cancer. The E6 and E7 papillomavirus proteins are normally required
for the maintenance of the malignant phenotype. Expression of these proteins in infected cells is negatively regulated by
the binding of the papilloma E2 protein to the long terminal control region of the papilloma virus genome. The E2 protein
can also promote cell arrest and apoptosis in HeLa cells. Therefore, it is clear that this protein has the potential of inhibiting
the malignant phenotype. Because, anticancer vaccines based in vaccinia viruses have recently been shown to be an effective
way to treat and to eradicate tumors, a recombinant vaccinia virus expressing the E2 gene of bovine papilloma virus (Modified
Vaccinia Ankara, MVA E2) was created, to explore further the antitumor potential of the E2 protein. A series of rabbits, containing
the VX2 transplantable papilloma carcinoma, were treated with MVA E2. An impressive tumor regression, up to a complete disappearance
of tumor, was observed in most animals (80%). In contrast, very little or no regression was detected if the normal vaccinia
virus was used. Lymphocytes isolated from MVA E2-treated rabbits did not show cytotoxic activity against tumor cells. However,
in these animals a humoral immune response against tumor cells was observed. These antitumor antibodies were capable of activating
macrophages to destroy tumor cells efficiently. These data indicate that injecting the MVA E2 recombinant vaccinia virus directly
into the tumor results in a robust and long-lasting tumor regression. Data also suggest that antitumor antibodies are responsible,
at least in part, for eliminating tumors by activating macrophage antibody-dependent cytotoxicity.
Received: 23 November 1999 / Accepted: 12 April 2000 |
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Keywords: | Macrophages Cytotoxicity Tumor immunity In vivo animal models |
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