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.

Institute of Molecular Genetics Academy of Sciences of the Czech Republic Prague

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Eur J Immunol. 2000 Dec;30(12):3723-31 PubMed

Eur J Immunol. 2001 Jan;31(1):250-8 PubMed

J Immunol. 1978 Jun;120(6):2027-32 PubMed

Br J Cancer. 2001 Feb 2;84(3):374-80 PubMed

Pharmacol Ther. 1996;69(1):1-14 PubMed

J Immunol. 1997 Mar 15;158(6):2723-30 PubMed

Int J Cancer. 1987 Apr 15;39(4):530-3 PubMed

J Clin Oncol. 2000 May;18(9):1954-9 PubMed

Cancer Res. 1987 Aug 15;47(16):4296-8 PubMed

Immunology. 1996 May;88(1):82-9 PubMed

Cancer Res. 1995 Oct 1;55(19):4404-8 PubMed

Anticancer Res. 1998 Mar-Apr;18(2A):813-7 PubMed

Int J Cancer. 1978 Mar 15;21(3):348-55 PubMed

J Clin Oncol. 1999 Jul;17(7):2105-16 PubMed

J Exp Med. 1993 Oct 1;178(4):1223-30 PubMed

Cancer Immunol Immunother. 1985;19(1):57-61 PubMed

Eur Cytokine Netw. 1999 Dec;10(4):541-8 PubMed

Int J Oncol. 1997 Jan;10(1):77-82 PubMed

Cancer Res. 1994 Jan 1;54(1):182-9 PubMed

J Immunol. 1996 May 1;156(9):3366-73 PubMed

Int J Oncol. 2001 Mar;18(3):475-8 PubMed

Gene Ther. 1996 Nov;3(11):944-5 PubMed

Int J Oncol. 1999 Mar;14(3):593-7 PubMed

Cancer J Sci Am. 2000 Feb;6 Suppl 1:S11-4 PubMed

Cancer Immunol Immunother. 2000 Apr;49(1):34-45 PubMed

Crit Rev Oncog. 1994;5(6):555-87 PubMed

Annu Rev Immunol. 1998;16:495-521 PubMed

J Immunol. 1994 Aug 15;153(4):1697-706 PubMed

Science. 1994 May 13;264(5161):961-5 PubMed