In the endeavour to develop a model for studying gene therapy of cancers associated with human papillomaviruses (HPVs), mouse cells were transformed with the HPV type 16 (HPV16) and activated H-ras oncogenes. This was done by cotransfection of plasmid p16HHMo, carrying the HPV16 E6/E7 oncogenes, and plasmid pEJ6.6, carrying the gene coding for human H-ras oncoprotein activated by the G12V mutation, into secondary C57BL/6 mouse kidney cells. An oncogenic cell line, designated MK16/1/IIIABC, was derived. The epithelial origin of the cells was confirmed by their expression of cytokeratins. No MHC class I and class II molecules were detected on the surface of MK16/1/IIIABC cells. Spontaneous metastases were observed in lymphatic nodes and lungs after prolonged growth of MK16/1/IIIABC-induced subcutaneous tumours. Lethally irradiated MK16/1/IIIABC cells induced protection against challenge with 10(5) homologous cells, but not against a higher cell dose (5 x 10(5)). Plasmids p16HHMo and pEJ6.6 were also used for preventive immunization of mice. In comparison with a control group injected with pBR322, they exhibited moderate protection, in terms of prolonged survival, against MK16/1/IIIABC challenge (P < 0.03). These data suggest that MK16/1/IIIABC cells may serve as a model for studying immune reactions against HPV16-associated human tumours.

• MeSH
• Cell Line MeSH
• Neoplasms, Experimental immunology   metabolism   pathology   MeSH
• Gene Expression MeSH
• Immunoblotting MeSH
• Immunohistochemistry MeSH
• Keratins analysis   MeSH
• Humans MeSH
• Neoplasm Metastasis pathology   MeSH
• Histocompatibility Antigens Class I metabolism   MeSH
• Histocompatibility Antigens Class II metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Tumor Cells, Cultured cytology   radiation effects   MeSH
• Oncogene Proteins, Viral genetics   MeSH
• Papillomaviridae genetics   MeSH
• Papillomavirus E7 Proteins MeSH
• Plasmids administration & dosage   genetics   immunology   MeSH
• Reverse Transcriptase Polymerase Chain Reaction MeSH
• Flow Cytometry MeSH
• ras Proteins genetics   metabolism   MeSH
• DNA, Recombinant MeSH
• Repressor Proteins * MeSH
• RNA genetics   metabolism   MeSH
• Transfection MeSH
• Cell Line, Transformed MeSH
• Neoplasm Transplantation MeSH
• Cell Transformation, Viral * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• E6 protein, Human papillomavirus type 16 MeSH Browser
• Keratins MeSH
• Histocompatibility Antigens Class I MeSH
• Histocompatibility Antigens Class II MeSH
• oncogene protein E7, Human papillomavirus type 16 MeSH Browser
• Oncogene Proteins, Viral MeSH
• Papillomavirus E7 Proteins MeSH
• ras Proteins MeSH
• DNA, Recombinant MeSH
• Repressor Proteins * MeSH
• RNA MeSH

Experiments were designed to examine whether local cytokine therapy of subcutaneous (s.c.) tumours results in inhibition of their lung metastases. Moderately immunogenic, major histocompatibility complex (MHC) class I and II negative. B7 negative, metastasizing murine carcinoma MK16 transplantable in syngeneic mice was obtained by co-transfection of human papilloma virus type 16 (HPV 16) E6/E7 and activated H-ras oncogene plasmid DNA into C57BL/6 kidney cells. After s.c. transplantation of the malignantly converted MK16 cells, the majority of the transplanted mice developed lung metastases; the number and size of the lung metastases increased with the increasing size of the s.c. tumour. Therapy of 5-day MK16 tumours by peritumoral administration of recombinant interleukin-2 (IL-2) and recombinant interleukin-12 (IL-12) inhibited growth of the s.c. MK16 tumour transplants and reduced the number of MK16 lung metastases. To investigate the antimetastatic effect of IL-2 and IL- 12 in a clinically more relevant setting, surgical minimal residual tumour disease was utilized. Subcutaneously growing MK16 carcinomas, 8-12 mm in diameter, were removed on day 30 and the operated mice were injected with IL-2 or IL- 12 on days 35-39 and 42-46 at the site of the operation. Treatment with IL-2 significantly reduced the percentage of MK16 tumour recurrences as well as the number of lung metastases, whereas the effect of IL- 12 was substantially weaker and statistically insignificant.

• MeSH
• B7-1 Antigen metabolism   MeSH
• B7-2 Antigen MeSH
• Cell Division drug effects   MeSH
• Antigens, CD metabolism   MeSH
• Histocompatibility Antigens metabolism   MeSH
• Tumor Virus Infections drug therapy   pathology   MeSH
• Papillomavirus Infections drug therapy   pathology   MeSH
• Interleukin-12 therapeutic use   MeSH
• Interleukin-2 therapeutic use   MeSH
• Carcinoma drug therapy   secondary   virology   MeSH
• Membrane Glycoproteins metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Lung Neoplasms drug therapy   secondary   MeSH
• Antineoplastic Agents therapeutic use   MeSH
• Cell Line, Transformed MeSH
• Neoplasm Transplantation MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• B7-1 Antigen MeSH
• B7-2 Antigen MeSH
• Antigens, CD MeSH
• Cd86 protein, mouse MeSH Browser
• Histocompatibility Antigens MeSH
• Interleukin-12 MeSH
• Interleukin-2 MeSH
• Membrane Glycoproteins MeSH
• Antineoplastic Agents MeSH