Single-batch production of recombinant human polyclonal antibodies

Mol Biotechnol. 2010 Jul;45(3):257-66. doi: 10.1007/s12033-010-9270-9.

Abstract

We have previously described the development and implementation of a strategy for production of recombinant polyclonal antibodies (rpAb) in single batches employing CHO cells generated by site-specific integration, the Sympress I technology. The Sympress I technology is implemented at industrial scale, supporting a phase II clinical development program. Production of recombinant proteins by site-specific integration, which is based on incorporation of a single copy of the gene of interest, makes the Sympress I technology best suited to support niche indications. To improve titers while maintaining a cost-efficient, highly reproducible single-batch manufacturing mode, we have evaluated a number of different approaches. The most successful results were obtained using random integration in a new producer cell termed ECHO, a CHO DG44 cell derivative engineered for improved productivity at Symphogen. This new expression process is termed the Sympress II technology. Here we describe proof-of-principle data demonstrating the feasibility of the Sympress II technology for single-batch rpAb manufacturing using two model systems each composed of six target-specific antibodies. The compositional stability and the batch-to-batch reproducibility of rpAb produced by the ECHO cells were at least as good as observed previously using site-specific integration technology. Furthermore, the new process had a significant titer increase.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies / genetics
  • Antibodies / immunology
  • Antibodies / metabolism*
  • Biotechnology / methods*
  • CHO Cells
  • Cell Culture Techniques / methods*
  • Clone Cells / metabolism
  • Cloning, Molecular / methods
  • Cricetinae
  • Cricetulus
  • Genetic Vectors
  • Humans
  • Protein Engineering
  • Recombinant Proteins / biosynthesis*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Respiratory Syncytial Viruses / immunology
  • Vaccinia / immunology

Substances

  • Antibodies
  • Recombinant Proteins