A new model of trispecific antibody resulting the cytotoxicity directed against tumor cells.
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.
Song
Li-Ping
LP
Institute of Genetics and Developmental Biology, the Chinese Academy of Sciences, Beijing 100101, China.
Cheng
Ju-Long
JL
Wang
Xiang-Bin
XB
Zhang
Zhong
Z
Fang
Min
M
Zhou
Zhi-Yong
ZY
Huang
Hua-Liang
HL
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*
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