title: Local cytokine treatment of HPV16-associated tumours results in inhibition of their lung metastases.
abstract: 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.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague.
authors.forename: R
authors.initials: R
authors.lastname: Mikysková
authors.forename: J
authors.initials: J
authors.lastname: Bubenik
authors.forename: L
authors.initials: L
authors.lastname: Mendoza
authors.forename: V
authors.initials: V
authors.lastname: Vonka
authors.forename: M
authors.initials: M
authors.lastname: Smahel
authors.forename: J
authors.initials: J
authors.lastname: Símová
authors.forename: T
authors.initials: T
authors.lastname: Jandlová
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary / Q000821:virology; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D005260:Female; D006649:Histocompatibility Antigens / Q000378:metabolism; D018664:Interleukin-12 / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D030361:Papillomavirus Infections / Q000188:drug therapy* / Q000473:pathology; D014412:Tumor Virus Infections / Q000188:drug therapy* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D018664:Interleukin-12