A new format of bispecific antibody: highly efficient heterodimerization, expression and tumor cell lysis.

Bispecific antibodies (BsAbs) have been considered as potential therapeutics for cancer. A major obstacle in the development of BsAb has been the difficulty in producing a heterodimer with two different arms and in sufficient quantity for clinical application by the traditional methods. We describe a new format of BsAb that consists of two single-chain variable fragment of antibodies (scFvs), one for human epidermal growth factor receptor 2 (HER2)/neu and the other for CD16, heterodimerized by a "knobs-into-holes" device from the CH3 domains of the human IgG1 Fc fragment. The two chains were functionally expressed in CHO cells and assembled into heterodimers with dual antigen-binding specificity. Compared with other types of engineered BsAbs expressed in mammalian cells, the yield of this BsAb was relatively high (12-14 mg/l). In vitro experiments demonstrated that the BsAb was able to recruit human peripheral blood mononuclear cells (PBMC) to kill SK-BR-3 cells more effectively than the commercial anti-HER2/neu antibody Herceptin (Roche, Shanghai). This new format of BsAb possesses properties that support its potential as a new antitumor agent.

Citation

Zhigang Xie, Ning Guo, Ming Yu, Meiru Hu, Beifen Shen. A new format of bispecific antibody: highly efficient heterodimerization, expression and tumor cell lysis. Journal of immunological methods. 2005 Jan;296(1-2):95-101

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PMID: 15680154

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