Addition of interleukin 12 to low dose interleukin 2 treatment improves antitumor efficacy in vivo.
Interleukin 12 (IL-12) enhances lysis mediated by NK- and lymphokine activated killer (LAK) cells. It also causes proliferation of IL-2 stimulated T and NK cells in vitro. For these IL-2 complementing properties murine pulmonary metastases of a coloncarcinoma line were treated with IL-12 and IL-2 or with the individual agents. Results were compared to sham treated controls. IL-2 alone mediated significant tumor reduction but provoked pulmonary edema and concomittand toxicity, graded in three steps. IL-12 combined with an IL-2 dose reduced by 81% still resulted in significant antitumoral activity. Toxicity, however, was not discernable from sham treated controls. IL-12 thus appears as an attractive cytokine for combination with IL-2 in antitumor therapy. Particularly treatment of tumors, like gastrointestinal tract cancers, so far mainly resistant to cell mediated antitumor therapy, might profit from this approach.
Department of Surgery, University of Ulm, USA.
G H
GH
Leder
M
M
Oppenheim
M
M
Rosenstein
M T
MT
Lotze
H G
HG
Beger
D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000633:toxicity; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000633:toxicity; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000627:therapeutic use / Q000633:toxicity
D007376:Interleukin-2; D011994:Recombinant Proteins; D018664:Interleukin-12