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.
Leder
G H
GH
Department of Surgery, University of Ulm, USA.
Oppenheim
M
M
Rosenstein
M
M
Lotze
M T
MT
Beger
H G
HG
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