title: A new model of trispecific antibody resulting the cytotoxicity directed against tumor cells.
abstract: Bispecific antibodies (BsAb) with specificity to both tumor cells and CD3 molecule were believed to be promising immunological tools for the therapy with minimal residual diseases by activating cytotoxic T cells. However, without costimulatory molecule CD28, the activated T cells tended to apoptosis. In order to kill tumor cells more efficiently, a recombinant multifunctional single-chain trispecific antibody (scTsAb), which contains anti-ovarian carcinoma (OC) scFv, anti-CD3 scFv and VH domain of anti-CD28 antibody, was constructed and expressed in E. coli BL21 Star strain. The scTsAb showed strong binding avidities to membrane antigen of SK-OV-3 cell, CD3 molecule on Jurkat cell, and recombinant CD28 antigen. It was further demonstrated that this scTsAb could activate peripheral blood T cells to elicit strong cytotoxicity against SK-OV-3 cells. This new type of recombinant scFv antibody set up a new technological platform for T cells based immunotherapy against cancer, especially with the failure on MHC antigen presentation or absence of costimulating signal.
authors.affiliation: Institute of Genetics and Developmental Biology, the Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Song
authors.forename: Ju-Long
authors.initials: JL
authors.lastname: Cheng
authors.forename: Xiang-Bin
authors.initials: XB
authors.lastname: Wang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Zhou
authors.forename: Hua-Liang
authors.initials: HL
authors.lastname: Huang
mesh_terms: D018033:Antibodies, Bispecific / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D019169:Jurkat Cells / Q000276:immunology; D008213:Lymphocyte Activation; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D018106:CD28 Antigens; D017252:CD3 Complex; D007135:Immunoglobulin Variable Region; D011993:Recombinant Fusion Proteins