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

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 anti-tumor 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.

• Authors: Q Hui, J Ma, J Song, Z Liu, H Ren, W Jiang, Y Wang, Y Xu, D Guo, X Zhang, S Lu
• Journal: Neoplasma (Neoplasma) Vol. 61 Issue 4 Pg. 392-400 ( 2014) ISSN: 0028-2685 [Print] Slovakia
• PMID: 25027740 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Bacterial Toxins
• Exotoxins
• Immunotoxins
• Recombinant Fusion Proteins
• Virulence Factors
• Melanocyte-Stimulating Hormones
• ADP Ribose Transferases
• Pseudomonas aeruginosa exotoxin A

Topics

• ADP Ribose Transferases (therapeutic use)
• Animals
• Antineoplastic Agents (therapeutic use)
• Bacterial Toxins (therapeutic use)
• Exotoxins (therapeutic use)
• Female
• Humans
• Immunoenzyme Techniques
• Immunotoxins (therapeutic use)
• In Vitro Techniques
• Liver Neoplasms (drug therapy, immunology, secondary)
• Melanocyte-Stimulating Hormones (immunology)
• Melanoma, Experimental (drug therapy, immunology, pathology)
• Mice
• Mice, Nude
• Recombinant Fusion Proteins (therapeutic use)
• Tumor Cells, Cultured
• Virulence Factors (therapeutic use)