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Enhanced production of anti-PD1 antibody in CHO cells through transient co-transfection with anti-apoptotic genes Bcl-x L and Mcl-1

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Abstract

Apoptosis has a negative impact on the cell survival state during cell cultivation. To optimize mammalian cell culture for production of biopharmaceuticals, one of the important approaches is to extend cell life through over-expression of anti-apoptotic genes. Here, we reported a cost-effective process to enhance cell survival and production of an antibody through transient co-transfection with anti-apoptotic genes Bcl-x L or Mcl-1 in Chinese hamster ovary (CHO) cells with polyethylenimine (PEI). Under the optimal conditions, it showed reduced levels of apoptosis and improved cell viability after co-transfected with Bcl-x L or Mcl-1. The overall production yield of the antibody anti-PD1 increased approximately 82% in CHO cells co-transfected with Bcl-x L , and 34% in CHO cells co-transfected with Mcl-1. This work provides an effective way to increase viability of host cells through delaying apoptosis onset, thus, raise production yield of biopharmaceuticals without the process of generating stable cell lines and subsequent screening.

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Acknowledgements

This project was supported by Natural Science Foundation of Shanghai [Grant No. 15ZR1423800].

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Authors and Affiliations

  1. Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education; School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People’s Republic of China

    Xinyu Zhang, Lei Han, Huifang Zong, Kai Ding, Yuan Yuan, Jingyi Bai, Yuexian Zhou, Baohong Zhang & Jianwei Zhu

  2. Jecho Laboratories, Inc. 7320 Executive Way, Frederick, MD, 21704, USA

    Jianwei Zhu

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  1. Xinyu Zhang
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Correspondence to Baohong Zhang or Jianwei Zhu.

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All the authors reviewed and agreed to submit this manuscript. The authors declare that they have no conflict of interest.

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449_2018_1898_MOESM1_ESM.tif

Supplement Fig. 1 Optimization of transfection efficiency in 3D plot showing the transfection efficiencies in CHO cells at different DNA: PEI ratios, DNA concentrations and cell concentrations. Samples were analyzed 48 h after transfection for GFP expression by flow cytometry (TIF 2139 KB)

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Zhang, X., Han, L., Zong, H. et al. Enhanced production of anti-PD1 antibody in CHO cells through transient co-transfection with anti-apoptotic genes Bcl-x L and Mcl-1. Bioprocess Biosyst Eng 41, 633–640 (2018). https://doi.org/10.1007/s00449-018-1898-z

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