Adeno-associated virus-mediated expression of kallistatin suppresses local and remote hepatocellular carcinomas.

Background: The current treatments for hepatocellular carcinoma (HCC) are poor, particularly for metastatic HCC. Intraportal transfusion of adeno-associated virus (AAV) leads to long-term and persistent transgenic expression in livers. Kallistatin, a novel angiogenesis inhibitor, exhibits anti-tumor activity.

Inhibition of angiogenesis and HCT-116 xenograft tumor growth in mice by kallistatin.

Aim: To investigate the inhibitory effect of kallistatin (KAL) on angiogenesis and HCT-116 xenograft tumor growth.

Methods: Heterotopic tumors were induced by subcutaneous injection of 2 multiply 10(6) HCT-11 cells in mice. Seven days later, 2 multiply 10(11) rAAV-GFP or rAAV-KAL was injected intratumorally (n = 5 for each group).

Anti-angiogenic therapy subsequent to adeno-associated-virus-mediated immunotherapy eradicates lymphomas that disseminate to the liver.

Liver cancer has a very poor prognosis and lacks effective therapy. We have previously demonstrated that intraportal injection of adeno-associated-viral (AAV) particles that express angiostatin lead to long-term expression of angiostatin capable of suppressing the outgrowth of EL-4 tumors in the liver. Here we combine AAV-mediated angiostatin therapy with immunotherapy by employing an AAV vector encoding the T-cell costimulator B7.