Enhanced therapeutic effect by combination of tumor-targeting Salmonella and endostatin in murine melanoma model.
The growth of tumor is angiogenesis-dependent and it often contains hypoxia and necrotic areas. Salmonella VNP20009 could target and replicate in hypoxia and necrotic areas within tumor and induce antitumor effect. Angiogenesis inhibitor endostatin could reduce tumor angiogenesis and inhibit its growth. However, in the phase I trials of VNP20009 and endostatin at the maximum-tolerated dose, no antitumor effects for bacteria therapy and minor therapeutic effects for endostatin treatment were seen. The ineffectiveness of these agents in clinical trials suggests that the combination of these agents with synergic modalities might be necessary. Here we described antitumor effects mediated by the combination of VNP20009 with recombinant human endostatin in B16F10 murine melanoma model with the aim to exploit tumor-targeting of bacteria and anti-angiogenesis strategy to enhance therapeutic efficacy. Combination therapy of these agents significantly enhanced antitumor effects by inducing greater tumor growth inhibition, more severe tumor tissue necrosis as well as less blood vessel density than those induced by either of treatments. The findings suggest that the combination of tumor-targeting bacteria with angiogenesis inhibitor might be of value for the treatment of solid tumors.
Jia
Li-Jun
LJ
The State Key Laboratory of Pharmaceutical Biotechnology and Department of Biochemistry, College of Life Sciences, Nanjing University, China.
Xu
Han-Mei
HM
Ma
Ding-Yuan
DY
Hu
Qin-Gang
QG
Huang
Xiao-Feng
XF
Jiang
Wen-Hui
WH
Li
Shu-Feng
SF
Jia
Kun-Zhi
KZ
Huang
Qi-Lai
QL
Hua
Zi-Chun
ZC
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001428:Bacterial Vaccines; D003131:Combined Modality Therapy; D043169:Endostatins / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000737:chemistry / Q000188:drug therapy*; D051379:Mice; D014613:Vaccines, Attenuated / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D020533:Angiogenesis Inhibitors; D001428:Bacterial Vaccines; D043169:Endostatins; C465023:VNP 20009; D014613:Vaccines, Attenuated; D042461:Vascular Endothelial Growth Factor A