title: Construction and characterization of a CTLA-4-targeted scFv-melittin fusion protein as a potential immunosuppressive agent for organ transplant.
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.
authors.affiliation: Institute for Organ Transplant Research, 309 Hospital of the Chinese People's Liberation Army, Beijing, 100091, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Jin
authors.forename: Congran
authors.initials: C
authors.lastname: Li
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Cai
authors.forename: Zhouli
authors.initials: Z
authors.lastname: Li
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Hong
authors.forename: Bingyi
authors.initials: B
authors.lastname: Shi
mesh_terms: D000818:Animals; D001483:Base Sequence; D060908:CTLA-4 Antigen / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology*; D000922:Immunotoxins / Q000494:pharmacology; D019169:Jurkat Cells; D008555:Melitten / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016377:Organ Transplantation; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D057127:Single-Chain Antibodies / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D060908:CTLA-4 Antigen; D007166:Immunosuppressive Agents; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; D008555:Melitten