Selexis CHO Cells in Suspension-1

Bispecifics

We are proud of the role that Selexis’ cell line technology is playing in helping to deliver on the promise of bispecifics, which is a rapidly expanding class of drugs showing impressive results in multiple clinical trials.

Selexis has both the technology platform and the scientific experience to address the productivity needs of almost any bi- or multispecfic therapeutic.

 

An "off-the-shelf" therapy that can be used immediately, rather than one that needs to be manufactured individually for each patient (such as chimeric antigen receptor T (CAR-T) cell therapies) and can be a life-saving proposition for patients facing difficult-to-treat diseases, such as many cancers. The promise of bispecific antibodies (bsAbs) comes from their “off-the-shelf” nature and their ability to recognize multiple targets simultaneously. While many of the bsAbs in development fundamentally maintain the heavy and light chain structure of standard antibodies, advances in protein engineering have allowed for development of smaller versions such as BiTEs and DARTs and for more complex versions with extra binding domains appended to the heavy and/or light chains of the antibodies.

For a manufacturing platform to be truly effective at making bsAbs, it should have three key features:

  1. Stable and high expression of the proteins of interest. In the case of bsAbs, that often means high-level expression of three to four different proteins simultaneously
  2. Have a straightforward way to screen early on for cell clones that make the highest levels of intact heterodimer and this typically requires screening of a panel of cells transfected with a matrixed panel of different heavy and light chain ratios
  3. Robust cell line to cope with any secretory stress resulting from translating, folding and pairing such complex, non-natural proteins leading to insufficient productivity

The Selexis’ SUREtechnology Platform™ provides a modular approach to cell line development that not only provides top cell line productivity levels in the industry, but also has sophisticated capabilities to address the myriad of challenges associated with producing complex difficult-to-express proteins, which bsAbs can be. To address the three key capabilities required for bsAbs production, the SUREtechnology Platform™ has:

  1. Selexis SGE®s (Selexis Genetic Elements): unique epigenetic DNA-based elements that control the dynamic organization of chromatin across all mammalian cells, allowing for enhanced transcription by isolating the integrated transgene from the silencing effects of the surrounding chromatin
  2. SUREvariant Screening™: Allows for the assessment of up to 250 different CHO-M cell transfectant pools (SUREpools™) expressing, for example, different ratios of the bsAb heavy and light chains.
  3. SURE CHO-Mplus Libraries™: for those cases where a bsAb product experiences secretion bottlenecks, these libraries were generated as a result of the genomic and transcriptomic analysis of Selexis’ CHO-M cell line. They allow Selexis to fine-tune secretion activities based on the specific secretory needs of a range of difficult-to-express proteins.