rIL-18 triggered gene therapy based on a transduction with the IL-12 plasmid: a new option as immuno-therapy for osteosarcoma?
Gene therapy is a promising new method to treat tumors locally. Immuno-therapy for treatment of osteosarcomas is one option for hopefully improving the survival rate of patients with this tumor. Transduction of OS cells with the pCMV-IL-12neo plasmid induced a significant increase in IFN-gamma expression by mononuclear cells. This is known to induce antitumor effects mediated by the immune system. In combination with an administration of rIL-18, the IFN-gamma increase was multiplied in a dose-dependent manner. This study demonstrated that osteosarcoma cells can be targeted effectively in vitro by plasmids encoding the IL-12 gene. Considering the synergistic pathways it is reasonable to combine a local, gene transfer based on IL-12 with a rIL-18 administration to trigger the potentially promising immuno-effects for adjuvant treatment of osteosarcomas.
Liebau
Christian
C
Department of Orthopaedic Surgery, Ernst-Moritz-Arndt University, Sauerbruchstrasse, 17487 Greifswald, Germany. baltzer@med.uni-duesseldorf.de
Merk
Harry
H
Roesel
Christian
C
Schmidt
Sebastian
S
Karreman
Christiaan
C
Prisack
Johannes Bernd
JB
Bojar
Hans
H
Baltzer
Axel W A
AW
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D003131:Combined Modality Therapy; D004357:Drug Synergism; D015316:Genetic Therapy / Q000379:methods*; D016233:Immunotherapy, Active / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D014161:Transduction, Genetic; D019076:Transgenes; D014407:Tumor Cells, Cultured
D020382:Interleukin-18; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma