In vitro and in vivo studies of antitumor effects of the recombinant immunotoxin MSH-PE38KDEL on melanoma

Q. HUI, J. MA, J. SONG, Z. LIU, H. REN, W. JIANG, Y. WANG, Y. XU, D. GUO, X. ZHANG, S. LU

Abstract:

MSH-PE38KDEL is a chimeric molecule composed of MSH, and fused to a truncated mutant form of Pseudomonas exotoxin (PE38KDEL). Our study aims to evaluate the specific cytotoxicity of recombinant immunotoxin MSH-PE38KDEL on melanoma cells A875 and B16 in vitro, as well as its inhibition of metastatic melanoma in vivo. MSH-PE38KDEL was expressed in Escherichia coli, and greater than 90% purity was obtained. The purified MSH-PE38KDEL was found to be selectively cytotoxic to MSH receptor-positive melanoma cells in vitro. The specific cytotoxicity of recombinant MSH-PE38KDEL to A875 and B16 was over 85% by cell viability assay; however, MSH-PE38KDEL had no cytotoxicity to the human 2BS cells. The anti­tumor activity of MSH-PE38KDEL was evaluated in mice with induced melanoma through intra-tumor or intravenous administration. The results showed that 90% melanoma growths were inhibited, and 40% of the tumors were disappeared completely. Histopathology results showed MSH-PE38KDEL can effectively inhibit intrahepatic metastasis. In conclusion, MSH-PE38KDEL had cytotoxic effects on MSH receptor-positive melanoma cells, and causes significant tumor growth inhibition. These results support a possible new approach for the treatment of melanoma.