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Cell Biochem Biophys. 2013;67(3):1067-74. doi: 10.1007/s12013-013-9605-9.

Construction and characterization of a CTLA-4-targeted scFv-melittin fusion protein as a potential immunosuppressive agent for organ transplant.

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  • 1Institute for Organ Transplant Research, 309 Hospital of the Chinese People's Liberation Army, Beijing, 100091, China.

Abstract

Immunotoxins with selective cytotoxicity are frequently used as therapeutic immunosuppressive agents in solid-organ transplantation because of their efficiency and high specificity. In this study, we present a new recombinant immunotoxin termed anti-CTLA-4-scFv-melittin prepared from Escherichia coli aimed at clearing activated T cells at the same time avoiding all-round decline in systematic immunity. This fusion protein is composed of anti-CTLA-4-scFv unit and melittin analog unit with properties of low immunogenicity and selective cytotoxicity to CTLA-4-positive T cells. In preliminary biological activity assays, our results confirmed the feasibility of activated T cell clearance strategy and there were significant differences in cell survival rates between CTLA-4-positive group and control group at all experimental concentrations of the immunotoxin. The selective cytotoxicity, low immunogenicity, and low production cost make it an attractive alternate to traditional immunosuppressants.

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