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. 2018 May;41(5):633-640. doi: 10.1007/s00449-018-1898-z. Epub 2018 Jan 25.

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.

Keywords: Anti-apoptosis; Bcl-x L; Chinese hamster ovary cell; Mcl-1; Transient gene expression.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetulus
  • Humans
  • Myeloid Cell Leukemia Sequence 1 Protein / biosynthesis*
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Programmed Cell Death 1 Receptor*
  • Single-Chain Antibodies / biosynthesis*
  • Single-Chain Antibodies / genetics
  • Transfection*
  • bcl-X Protein / biosynthesis*
  • bcl-X Protein / genetics

Substances

  • BCL2L1 protein, human
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Single-Chain Antibodies
  • bcl-X Protein