Effective antitumour mono- and combination therapy by gene delivery of angiostatin-like molecule and interleukin-12 in a murine hepatoma model.
METHODS
We applied an experimental approach employing two recombinant adenoviral vectors (Ad) that express interleukin-12 (IL-12) and angiostatin-like molecule (K1-3) respectively to a subcutaneous hepatoma model in mice.


RESULTS
Injection of AdK1-3 into tumour nodules established by subcutaneous (s.c.) implantation of Hepa129 hepatoma cells in C3H mice resulted in a significant dose-dependent reduction in tumour growth by 57% in the high dosage group (5x10(9) plaque-forming units [pfu], n=8) 10 days after treatment initiation. Similar antitumoural effects were found for the intratumoural mono-therapy with IL-12 (2.5x10(9) pfu, n=8) resulting in 60% tumour inhibition at the same time point. The survival rate was significantly (p=0.009) improved in the IL-12 but not in the K1-3 treatment group. A combination therapy of AdK1-3 and AdIL-12 was also effective, but did not further improve antitumour efficacy compared with the monotherapy.


CONCLUSIONS
In conclusion, both mono- and combination therapy of K1-3 and IL-12 significantly inhibited tumour progression in this experimental tumour model. The co-administration of both compounds did not result in additive antitumour effects. We hypothesise that the lack of additive antitumour effects of the combination treatment might be attributed to partially counteracting antitumour effects and further studies are needed to illustrate the interference of tumour angiogenesis and tumour inflammation in this tumour model.
Schmitz
Volker
V
Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany. Volker.Schmitz@ukb.uni-bonn.de
Tirado-Ledo
Lucia
L
Raskopf
Esther
E
Rabe
Christian
C
Wernert
Nicolas
N
Wang
Lin
L
Prieto
Jesús
J
Qian
Cheng
C
Sauerbruch
Tilman
T
Caselmann
Wolfgang H
WH
D000256:Adenoviridae / Q000235:genetics; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D043168:Angiostatins / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D015552:Injections, Intralesional; D018664:Interleukin-12 / Q000008:administration & dosage / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D018664:Interleukin-12; D043168:Angiostatins