A recombinant vaccinia virus containing the papilloma E2 protein promotes tumor regression by stimulating macrophage antibody-dependent cytotoxicity

Human papillomavirus infection is associated with cervical cancer. The Eb a nd 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 clea r 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 recombina nt vaccinia virus expressing the E2 gene of bovine papilloma virus (Modifie d Vaccinia Ankara, MVA E2) was created, to explore further the antitumor po tential of the E2 protein. A series of rabbits, containing the VX2 transpla ntable papilloma carcinoma, were treated with MVA E2. An impressive tumor r egression, up to a complete disappearance of tumor, was observed in most an imals (80%). In contrast, very little or no regression was detected if the normal vaccinia virus was used. Lymphocytes isolated from MVA E2-treated ra bbits did not show cytotoxic activity against tumor cells. However, in thes e animals a humoral immune response against tumor cells was observed. These antitumor antibodies were capable of activating macrophages to destroy tum or cells efficiently, These data indicate that injecting the MVA E2 recombi nant vaccinia virus directly into the tumor results in a robust and long-la sting tumor regression. Data also suggest that antitumor antibodies are res ponsible, at least in part, for eliminating tumors by activating macrophage antibody-dependent cytotoxicity.