Immunotherapy by gene transfer with plasmids encoding IL-12/IL-18 is superior to IL-23/IL-18 gene transfer in a rat osteosarcoma model.
BACKGROUND
Osteosarcomas are primary malignant tumors of bone or soft parts arising from bone-forming mesenchymal cells. Despite dramatic therapeutic advances, namely neo-adjuvant and adjuvant chemotherapy, progress is at a plateau. Cytokine-mediated gene therapy might represent a further advance in the therapy of the osteosarcoma.


METHODS
We transfected UMR 108 osteosarcoma cells with different plasmids encoding IL-12, IL-23, proIL-18 and ICE (Interleukin-converting enzyme). IFN-gamma induction, which is known to induce antitumor effects mediated by the immune system, and cytotoxic effects of various cytokine combination were investigated.


RESULTS
Our results show that local secretion of IL-12 by UMR 108 cells led to an induction of cytotoxic effects mediated by mononuclear cells, which were enhanced by additional administration of recombinant IL-18. In contrast to IL-18, IL-23 showed a moderate increase of IFN-gamma induction when transfected alone and could only slightly increase the IFN-gamma induction mediated by IL-12. IL-18 enhanced IFN-gamma induction when applied alone and was able to increase the IFN-gamma production that was induced by IL-12.


CONCLUSIONS
IL-23 seems to be a less effective immuno-therapeutic for adjuvant treatment of osteosarcomas than IL-12 and IL-18, when taking only IFN-gamma induction into consideration.
Liebau
Christian
C
Department of Orthopaedic Surgery, Asklepios Clinic, 38667 Bad Harzburg, Germany.
Roesel
Christian
C
Schmidt
Sebastian
S
Karreman
Christiaan
C
Prisack
Johannes Bernd
JB
Bojar
Hans
H
Merk
Harry
H
Wolfram
Neumann
N
Baltzer
Axel W A
AW
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D012516:Osteosarcoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
C508842:Il23a protein, rat; D020382:Interleukin-18; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma; D020170:Caspase 1