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Bispecific antibody and its clinical applications in cancer

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Chinese Science Bulletin

Abstract

Bispecific antibody (BsAb) usually consists of two different antigen-binding arms, by which it is capable of simultaneously binding to target cells and effector cells, and can directly mediate the killing of target cells by retargeting and activating effector cells. The development of BsAb research goes through three main stages: chemical crosslinking of murine-derived monoclonal antibody, hybrid hybridomas and engineered BsAb. Among them, engineered BsAb has more formats than the other two, such as diabody, ScdHLX, ScZip, ScCH3, ScFab and BsIgG, etc. Compared with former murine-derived BsAbs, engineered BsAb has lower immunogenicity and stronger penetrating capacity, and currently, some of them appear suitable for clinical application in yields and qualities. Up to now, several phase I and phase II clinical studies of BsAb, for instance, some (Fab’)2 and Diabodies, have been performed. Among those BsAbs, anti-CD3/anti-tumor BsAbs is most common, they not only can activate T cell and induce CD3AK cytotoxic activity inin vitro experiment, and inhibit the growth of tumor on tumor-bearing mouse by retargeting T cells to lyse tumor cells, but also offer great promise in the therapy of some malignancies in clinic, especially of some advanced cancers as well as elimination of minimal residual tumors, indicated by increasing the tumor/blood ratio of antibody in patients and improving the natural killer cell (NK) anti-tumor activity in tumor sites, and also presenting of an increase level in TNF-α, INF-γ, IL-6, IL-8, IL-10 and soluble CD25, etc. The responses are also shown via improving the quality of life and prolonging the survival of partial patients. The “Knobs into Holes” technology is a new strategy emerging during research on engineered BsAb, it is likely to be useful for heterodimerization and can improve the quantity, purity and stability of BsAb, it is also anticipated to increase the clinical potential of BsAb in the future.

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Authors and Affiliations

  1. National Laboratory of Experiment Hematology, Institute of Hematology, Peking Union Medical College, Chinese Academy of Medical Science, 300020, Tianjin, China

    Yuanfu Xu, Chunzheng Yang & Zhenping Zhu

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  1. Yuanfu Xu
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  2. Chunzheng Yang
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  3. Zhenping Zhu
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Correspondence to Yuanfu Xu.

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Xu, Y., Yang, C. & Zhu, Z. Bispecific antibody and its clinical applications in cancer. Chin.Sci.Bull. 46, 353–358 (2001). https://doi.org/10.1007/BF03183262

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  • DOI: https://doi.org/10.1007/BF03183262

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