Tumour-inhibitory and antimetastatic effects of IL-2 in mice carrying MHC class I- tumours of HPV16 origin.

Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
International Journal of Oncology (Impact Factor: 3.03). 04/2002; 20(3):643-6. DOI: 10.3892/ijo.20.3.643
Source: PubMed


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.

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    • "Due to the redundancy of direct priming of CD8 + CTLs and tumour antigen cross-priming through dendritic cells, even MHC class I ñ tumour cells can induce MHC class I-restricted CTLs. However, the MHC class I ñ tumour cells will not bind the induced CTLs and will not be destroyed by them, unless MHC class I molecule expression is upregulated on the tumour targets (Indrov· et al., 2002). Despite the MHC class I molecule deficiences and the resulting resistance of the MHC class I ñ tumours to the CD8 + CTLs, in the HPV 16-related and some other experimental tumour systems the tumour hosts were found to be capable of being immunized against MHC class I ñ tumours (for review, see BubenÌk, 2002). "
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