Combined anti-tumor efficacy of somatostatin fusion protein and vaccinia virus on tumor cells with high expression of somatostatin receptors

Abstract

Somatostatin, a growth hormone-release inhibiting peptide, exerts antiproliferative and antiangiogenic effects on tumor cells. However, the short half-life of somatostatin limits its application in human therapy, and long-acting somatostatin fusion protein is also limited by its severe terminal degradation. Therefore, oncolytic virus delivery system was introduced to express somatostatin fusion protein and the anti-tumor effects of both somatostatin and oncolytic virus were combined to destroy tumor tissues. Here, a vaccinia VG9/(SST-14)2-HSA recombinant was constructed by replacing somatostatin fusion gene into TK locus of attenuated VG9 strain via homologous recombination. Results showed that vaccinia VG9/(SST-14)2-HSA possessed a combined anti-tumor effect on sstr-positive tumor cells in vitro. In the tumor burden models, BALB/c mice with complete immunity are most suitable for evaluating tumor regression and immune activation. Complete tumor regression was observed in 3 out of 10 mice treated with vaccinia VG9/TK− or VG9/(SST-14)2-HSA, and the survival of all mice in both groups was significantly prolonged. Besides, vaccinia VG9/(SST-14)2-HSA is more effective in prolonging survival than VG9/TK−. Vaccinia VG9/(SST-14)2-HSA exerts a combined anti-tumor efficacy including the oncolytic ability provided by the virus and the anti-tumor effect contributed by (SST-14)2-HSA, which is expected to become a potent therapeutic agent for cancer treatment.