Human tumor growth is inhibited by a vaccinia virus carrying the E2 gene of bovine papillomavirus

BACKGROUND. Papillomavirus is the etiologic agent associated with cervical carcinoma. The papilloma E2 protein is able to regulate negatively the expr ession of E6 and E7 papilloma oncoproteins. Therefore, a new highly attenua ted vaccinia virus known as modified vaccinia virus Ankara (MVA), which car ries the papillomavirus E2 gene, was used for the treatment of tumors assoc iated with human papillomavirus. METHODS. Analysis of expression of the E2 gene from the recombinant vaccini a virus was performed by reverse transcription-polymerase chain reaction of RNA isolated from infected cells. Detection of the E2 protein was done by immunoprecipitation from proteins labeled with [S-35]-methionine, isolated from infected cells. The therapeutic effect of the MVA E2 recombinant virus over human tumors was tested in nude mice bearing tumors generated by inoc ulation of HeLa cells. Series of 10 nude mice with tumors of different size s were injected with MVA, MVA E2, or phosphate-buffered saline. Tumor size was monitored every week to assess growth. RESULTS. The MVA E2 recombinant virus efficiently expressed the E2 protein in BS-C-I cells. This protein was able to repress, in vivo, the papillomavi rus P105 promoter, which controls the expression of the EG and E7 oncoprote ins. In nude mice the MVA E2 virus reduced tumor growth very efficiently. I n contrast, tumors continued to grow in mice treated with MVA or PBS. The L ife expectancy of MNA E2-treated mice was also increased three- to fourfold compared with that of animals that received MVA or PBS. CONCLUSIONS. The growth of human turners was efficiently inhibited by the M VA E2 recombinant vaccinia virus. The absence of side effects in treated an imals suggested that the MVA E2 virus is a safe biologic agent that could i n the future be used in humans for the treatment of cervical carcinoma. (C) 2000 American Cancer Society.