title: Capacity of murine IL-12 to inhibit the development of primary melanoma tumors and to prevent lung metastases in the melanoma-challenged mice.
abstract: Interleukin-12 (IL-12) has the capacity to activate cytotoxic lymphocytes, stimulate natural killer cells, induce the production of INF-gamma, and be synergistic with IL-2. We have evaluated this cytokine in an experimental model for metastatic melanoma that approximates the major clinical stages of metastatic dissemination. To develop primary melanoma tumors, mice were injected subcutaneously with 5 x 10(5) cells in a volume of 25 microliters into the middle of the tail (11). In a month, mice were started to be treated for 4 weeks with recombinant murine IL-12 (R mIL-12) at the following doses: 0, 0.5, 2.5, 5.0, 15.0, and 50 micrograms/kg. Diameters of the primary melanoma tumors were measured at weekly intervals. At the end of 13 weeks (9 weeks from the start of treatment with R mIL-12), all surviving mice were sacrificed. Pathological examination of lung metastases (macroscopy) was done with all dead or sacrificed mice. Treatment of mice bearing melanoma at a dose of 300 ng/mouse (15 micrograms/kg) inhibited development of primary tumors in 40% of mice. The primary tumor diameters were significantly lower in the group treated with 300 ng/mouse (15 micrograms/kg) in comparison to controls. At the end of the observation period, groups treated with 0.5, 2.5, 15.0, and 50 micrograms/kg had mean primary tumor diameters smaller than the control group. Evaluation of IL-12 therapy on primary tumor growth, mean diameters of primary tumors, survival rate, and development of lung metastases showed that the best results were observed using 300 ng/mouse (15 micrograms/kg) R mIL-12.
authors.affiliation: Departments of Surgery and Pathology, Roger Williams Medical Center, Brown University, 825 Chalkstone Avenue, Providence, RI 02908, USA. David_Shrayer@brown.edu
authors.forename: David P
authors.initials: DP
authors.lastname: Shrayer
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bogaars
authors.forename: Bernard
authors.initials: B
authors.lastname: Cole
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Wolf
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Wanebo
mesh_terms: D000818:Animals; D018664:Interleukin-12 / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000556:secondary*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D015996:Survival Rate
chemical_list: D018664:Interleukin-12