BACKGROUND/AIMS: B7H3 immunogene therapy is able to completely eradicate tumors when combined with an anti-vascular agent. The aim of this study was to determine whether vasostatin, a potent anti-angiogenic agent, could synergize with B7H3-mediated immunotherapy to combat hepatocellular carcinoma (HCC). METHODS: Vasostatin and B7H3 expression plasmids were constructed, and the in vitro and in vivo expression and anti-angiogenic activity of recombinant vasostatin were measured. The anti-tumor activities of B7H3 and vasostatin alone and in combination were assessed using single and multiple H22 tumor models. RESULTS: Gene transfer of vasostatin inhibited the proliferation of aortic endothelial cells, and angiogenesis in the chorioallantoic membrane assay. Subcutaneous H22 tumors established in BALB/c mice were completely eradicated in response to intratumoral injection of B7H3-expressing plasmids followed 24h later by vasostatin-expressing plasmids. In contrast, neither vasostatin nor B7H3 monotherapy was effective. Gene transfer of vasostatin inhibited tumor angiogenesis and enhanced infiltration of NK cells, whereas B7H3 therapy activated CD8+ and NK cells and increased their infiltration into tumors, and enhanced the levels of circulating IFN-gamma. B7H3 and vasostatin combination gene therapy was effective in combating a systemic challenge of parental H22 cells, and caused the complete regression of multiple distant tumor nodules. CONCLUSIONS: Combining vasostatin anti-angiogenic therapy with B7H3-mediated immunotherapy warrants investigation as a therapeutic strategy to combat HCC, and other malignancies.
BACKGROUND/AIMS: B7H3 immunogene therapy is able to completely eradicate tumors when combined with an anti-vascular agent. The aim of this study was to determine whether vasostatin, a potent anti-angiogenic agent, could synergize with B7H3-mediated immunotherapy to combat hepatocellular carcinoma (HCC). METHODS: Vasostatin and B7H3 expression plasmids were constructed, and the in vitro and in vivo expression and anti-angiogenic activity of recombinant vasostatin were measured. The anti-tumor activities of B7H3 and vasostatin alone and in combination were assessed using single and multiple H22 tumor models. RESULTS: Gene transfer of vasostatin inhibited the proliferation of aortic endothelial cells, and angiogenesis in the chorioallantoic membrane assay. Subcutaneous H22 tumors established in BALB/c mice were completely eradicated in response to intratumoral injection of B7H3-expressing plasmids followed 24h later by vasostatin-expressing plasmids. In contrast, neither vasostatin nor B7H3 monotherapy was effective. Gene transfer of vasostatin inhibited tumor angiogenesis and enhanced infiltration of NK cells, whereas B7H3 therapy activated CD8+ and NK cells and increased their infiltration into tumors, and enhanced the levels of circulating IFN-gamma. B7H3 and vasostatin combination gene therapy was effective in combating a systemic challenge of parental H22 cells, and caused the complete regression of multiple distant tumor nodules. CONCLUSIONS: Combining vasostatin anti-angiogenic therapy with B7H3-mediated immunotherapy warrants investigation as a therapeutic strategy to combat HCC, and other malignancies.
Authors: Neal Luther; Nai-Kong Cheung; Eleni P Souliopoulos; Ioannis Karampelas; Ioannis Karempelas; Daniel Bassiri; Mark A Edgar; Hong-Fen Guo; Ira Pastan; Philip H Gutin; Mark M Souweidane Journal: Mol Cancer Ther Date: 2010-04-06 Impact factor: 6.261
Authors: Michael R Garbati; Catherine A Welgan; Sally H Landefeld; Laura F Newell; Anupriya Agarwal; Jennifer B Dunlap; Tapan K Chourasia; Hyunjung Lee; Johannes Elferich; Elie Traer; Rogan Rattray; Michael J Cascio; Richard D Press; Grover C Bagby; Jeffrey W Tyner; Brian J Druker; Kim-Hien T Dao Journal: Am J Hematol Date: 2016-02 Impact factor: 10.047