The novel fusion protein sTRAIL-TMTP1 exhibits a targeted inhibition of primary tumors and metastases

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively kill tumor cells and enhance therapy in vivo. However, concerns regarding its considerable liver toxicity limit its use in humans as a cancer therapy. Tumor molecular targeted peptide 1 (TMTP1) has previously been reported by our laboratory to target primary tumors and metastatic foci. Here, we report a novel recombinant fusion protein, sTRAIL-TMTP1, which not only induced apoptosis in cancer cells in vitro but also inhibited tumor growth and metastases in vivo. Moreover, sTRAIL-TMTP1 impacted tumor angiogenesis. The biodistribution results demonstrated that sTRAIL-TMTP1 accumulation peaked 6 h after injection and persisted for 24 h in the tumor, while faint sTRAIL-TMTP1 accumulation was detected in normal organs in tumor-bearing mice. Thus, combining sTRAIL with TMTP1 resulted in high anti-tumor activity and low toxicity. In conclusion, the novel fusion protein sTRAIL-TMTP1 was successfully developed in our laboratory and was observed to induce apoptosis both in primary and metastatic cancer, which may lead to the development of novel, targeted anticancer agents.