Augmented antitumor effects of combination therapy with interleukin-12, cisplatin, and tumor necrosis factor-alpha in a murine melanoma model.
Interleukin-12 (IL-12) has demonstrated antitumor activity in many murine tumor models. However, toxic effects resulting from treatment with IL-12 have been also described. Combining IL-12 with other antineoplastic agents could potentiate its antitumor efficacy and, furthermore, could minimize its toxicity by reducing the doses necessary to achieve the antitumor activity. We examined in a murine melanoma model the efficacy of combination tumor chemo-immunotherapy based on administration of IL-12, cisplatin (CDDP), and tumor necrosis factor-alpha (TNF-alpha). In the current study pairs of: IL-12 + CDDP and IL-12 + TNF-alpha, showed stronger antitumor activity than either agent given alone. Furthermore, combination tumor therapy with IL-12 + CDDP + TNF-alpha was more effective at retarding local tumor growth than either IL-12 + CDDP, IL-12 + TNF-alpha or CDDP + TNF-alpha combination therapies. Our observations indicate that combining of CDDP with IL-12 and IL-12 with TNF-alpha as well as using the triple combination of CDDP, IL-12 and TNF-alpha could be beneficial in tumor therapy.
Zagozdzon
R
R
Department of Immunology, Medical School of Warsaw, Poland.
Stokłosa
T
T
Gołab
J
J
Giermasz
A
A
Dabrowska
A
A
Lasek
W
W
Jakóbisiak
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004357:Drug Synergism; D007167:Immunotherapy; D018664:Interleukin-12 / Q000627:therapeutic use*; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D002945:Cisplatin