title: Tumour-inhibitory and antimetastatic effects of IL-2 in mice carrying MHC class I- tumours of HPV16 origin.
abstract: Oncogenic, moderately immunogenic, MHC class I- and class II-, B7-, MK16/1/III ABC (MK16) cells were previously established by co-transfection of HPV16 E6/E7 and activated H-ras oncogene DNA into C57BL/6 kidney cells. Subcutaneous transplantation of these cells produced progressively growing local neoplasms which metastasized spontaneously to lungs and lymph nodes. The MK16 cells were implanted into syngeneic mice and used to examine whether the tumour lacking the signal molecules required for the induction of and sensitivity to T cell immunity is susceptible to local IL-2 treatment and IL-2 gene therapy. Peritumoural administration of human rIL-2 or murine IL-2 gene-modified MK16 tumour vaccine inhibited growth of subcutaneous MK16 tumour transplants and reduced the number of their lung metastases. Spleen cells from MK16 tumour-immunized mice were not cytolytic when allowed to react with the MK16 target cells, although they efficiently lysed the MHC class I+ malignant TC1 cells, obtained from C57BL/6 lung cell cultures after transfection with the same plasmids as those used for the derivation of the MK16 cells. However, when the MK16 cells were cultivated in vitro in the presence of IFNgamma, they acquired, together with the expression of MHC class I molecules, the sensitivity to the cytolytic effect of spleen cells from the MK16 tumour-immunized mice. These results indicate that experimental tumours which are MHC class I- and mimick in this respect a high proportion of human HPV16-associated carcinomas are suitable for IL-2 treatment.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Indrová
authors.forename: Jan
authors.initials: J
authors.lastname: Bubeník
authors.forename: Romana
authors.initials: R
authors.lastname: Mikysková
authors.forename: Vladimír
authors.initials: V
authors.lastname: Vonka
authors.forename: Michal
authors.initials: M
authors.lastname: Smahel
authors.forename: Roman
authors.initials: R
authors.lastname: Zák
authors.forename: Jana
authors.initials: J
authors.lastname: Símová
authors.forename: Jana
authors.initials: J
authors.lastname: Bieblová
authors.forename: Luis
authors.initials: L
authors.lastname: Mendoza
authors.forename: Tána
authors.initials: T
authors.lastname: Jandlová
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D027383:Papillomaviridae / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D007376:Interleukin-2