Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis.

Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print Cited Medium: Print ISSN: 0021-9738 (Print) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE

Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.

Cytokines/*immunology ; Interleukin-12/*immunology ; Neoplasms, Experimental/*blood supply ; Neoplasms, Experimental/*immunology ; Neovascularization, Pathologic/*immunology; Animals ; Antibodies, Blocking/immunology ; Cytokines/genetics ; Cytokines/metabolism ; Cytotoxicity Tests, Immunologic ; Female ; Gene Expression ; Genetic Vectors ; Interferon-gamma/immunology ; Interferon-gamma/metabolism ; Interleukin-12/genetics ; Interleukin-12/metabolism ; Interleukin-18 ; Mice ; Mice, SCID ; Neoplasm Transplantation/immunology ; Neoplasms, Experimental/pathology ; Neovascularization, Pathologic/pathology ; Neutralization Tests ; Spleen/cytology ; Spleen/immunology ; Transduction, Genetic ; Tumor Cells, Cultured/metabolism

The antitumor effect and mechanisms activated by murine IL-12 and IL-18, cytokines that induce IFN-gamma production, were studied using engineered SCK murine mammary carcinoma cells. In syngeneic A/J mice, SCK cells expressing mIL-12 or mIL-18 were less tumorigenic and formed tumors more slowly than control cells. Neither SCK.12 nor SCK.18 cells protected significantly against tumorigenesis by distant SCK cells. However, inoculation of the two cell types together synergistically protected 70% of mice from concurrently injected distant SCK cells and 30% of mice from SCK cells established 3 d earlier. Antibody neutralization studies revealed that the antitumor effects of secreted mIL-12 and mIL-18 required IFN-gamma. Interestingly, half the survivors of SCK.12 and/or SCK.18 cells developed protective immunity suggesting that anti-SCK immunity is unlikely to be responsible for protection. Instead, angiogenesis inhibition, assayed by Matrigel implants, appeared to be a property of both SCK.12 and SCK.18 cells and the two cell types together produced significantly greater systemic inhibition of angiogenesis. This suggests that inhibition of tumor angiogenesis is an important part of the systemic antitumor effect produced by mIL-12 and mIL-18.

J Immunol. 1994 May 1;152(9):4242-54. (PMID: 7908914)
J Immunol. 1994 Aug 15;153(4):1697-706. (PMID: 7913943)
Cell. 1994 Oct 21;79(2):315-28. (PMID: 7525077)
Eur J Immunol. 1995 Jan;25(1):137-46. (PMID: 7843224)
Eur J Immunol. 1995 Mar;25(3):672-6. (PMID: 7705395)
J Natl Cancer Inst. 1995 Apr 19;87(8):581-6. (PMID: 7538593)
J Immunol. 1995 Jun 15;154(12):6466-74. (PMID: 7759882)
J Exp Med. 1995 Jul 1;182(1):155-62. (PMID: 7540647)
Annu Rev Immunol. 1995;13:251-76. (PMID: 7612223)
Cancer Res. 1995 Nov 1;55(21):4980-7. (PMID: 7585539)
Nature. 1995 Nov 2;378(6552):88-91. (PMID: 7477296)
Am J Pathol. 1995 Dec;147(6):1693-707. (PMID: 7495294)
Blood. 1996 May 1;87(9):3877-82. (PMID: 8611715)
J Invest Dermatol. 1996 May;106(5):1114-8. (PMID: 8618049)
Cancer Res. 1996 Jun 1;56(11):2531-4. (PMID: 8653692)
Am J Pathol. 1997 May;150(5):1869-80. (PMID: 9137109)
Annu Rev Immunol. 1997;15:749-95. (PMID: 9143706)
Cancer Res. 1997 Jun 15;57(12):2460-7. (PMID: 9192826)
J Natl Cancer Inst. 1997 Jul 16;89(14):1049-58. (PMID: 9230887)
Br J Cancer. 1980 Feb;41(2):309-12. (PMID: 7370172)
Biochemistry. 1982 Nov 23;21(24):6188-93. (PMID: 6217835)
Immunol Rev. 1992 Jun;127:5-24. (PMID: 1387110)
Lab Invest. 1992 Oct;67(4):519-28. (PMID: 1279270)
Science. 1993 Apr 23;260(5107):547-9. (PMID: 8097338)
J Exp Med. 1993 Jun 1;177(6):1779-84. (PMID: 7684434)
Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5687-90. (PMID: 7685909)
Cancer Res. 1994 Jan 1;54(1):182-9. (PMID: 7903204)
J Immunol. 1996 Jun 1;156(11):4274-9. (PMID: 8666798)
Eur J Immunol. 1996 Jul;26(7):1647-51. (PMID: 8766574)
Int Immunol. 1996 Jun;8(6):855-65. (PMID: 8671675)
Cell. 1996 Aug 9;86(3):353-64. (PMID: 8756718)
Cancer Res. 1996 Aug 1;56(15):3399-403. (PMID: 8758901)
J Immunol. 1996 Nov 1;157(9):3967-73. (PMID: 8892629)
Cell. 1997 Jan 24;88(2):277-85. (PMID: 9008168)
Cancer Immunol Immunother. 1997 Jan;43(6):361-7. (PMID: 9067408)
J Immunol. 1997 Apr 1;158(7):3359-65. (PMID: 9120294)
Blood. 1997 Apr 15;89(8):2635-43. (PMID: 9108380)
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3948-53. (PMID: 9108085)

0 (Antibodies, Blocking)
0 (Cytokines)
0 (Interleukin-18)
187348-17-0 (Interleukin-12)
82115-62-6 (Interferon-gamma)

Date Created: 19980429 Date Completed: 19980423 Latest Revision: 20181113

20240829

PMC508700

10.1172/JCI1555

9502787