Purified anti-CD3 × anti-HER2 bispecific antibody potentiates cytokine-induced killer cells of poor spontaneous cytotoxicity against breast cancer cells

Cell & Bioscience

Wei Ge⁴  Xuetao Cao⁴  Wenhua Yu¹  Hong Hoi Ting²  Youzhao Wang⁴  Haisong Zhang³  Qingzhong He⁴ 

[1] National Key Laboratory of Medical Molecular Biology & Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Dongdan Santiao 5 #, Dongcheng district, Beijing 100005, China;JiangSu Laitai Medical Biotechnology Co., LTD, 3F, Building4, No.879 Zhongjiang Road, Shanghai, China;Affiliated Hospital of Hebei University, No.212, Yu Hua East Rd, Nan Shi District, Baoding, Hebei 071000, China;National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Dongdan Santiao 5 #, Dongcheng district, Beijing 100005, China

关键词: Protein purification;    Chemical crosslinking;    CIK cells;    Bispecific antibody;   

Others  :  1135317
DOI  :  10.1186/2045-3701-4-70

 received in 2014-09-01, accepted in 2014-11-07,  发布年份 2014

【 摘 要 】

Background

Chemical crosslinking is the most straightforward method to produce bispecific antibodies (BsAb) for arming ex vivo activated cytotoxic T lymphocytes. However, heterogeneous polymers are produced by chemical crosslinking. Currently, it is not known under what circumstances or to what extent further purification is needed.

Results

In this study, we purified Traut’s Reagent-Sulfo-SMCC crosslinked anti-CD3 × anti-HER2 by size-exclusion column chromatography and compared the capacity of the crude and the purified forms of the BsAb in enhancing cytokine-induced killer (CIK) cell-mediated cytotoxicity in vitro. We found that the purified BsAb assisted CIK cells more efficiently than the crude form only when the spontaneous cytotoxicity of the CIK cells was relatively low; otherwise, the two forms performed almost identically.

Conclusions

For the CIK cells of low spontaneous cytotoxicity, purified BsAb is a more powerful substitute for crude BsAb in enhancing their killing efficacy. However, that purification of BsAb is not necessary for robust CIK cells. This phenomenon also corroborates that CIK-mediated cytotoxicity is highly dependent on cell contact.

【 授权许可】

   
2014 He et al.; licensee BioMed Central Ltd.

【 图 表 】

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