A New Model of
Trispecific Antibody Resulting the Cytotoxicity Directed against Tumor Cells
SONG Li-Ping, CHENG Ju-Long, WANG Xiang-Bin, ZHANG Zhong, FANG Min,
ZHOU Zhi-Yong, HUANG Hua-Liang*
(
Institute of Genetics and Developmental Biology, the Chinese Academy of
Sciences, Beijing 100101, China )
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.
Key words trispecific
antibody (TsAb); scFv; ovarian carcinoma (OC); CD3; CD28
*Corresponding
author: Tel, 86-10-64857285; Fax, 86-10-64857285;
e-mail, [email protected]