FAST SPEED, HIGH TITER, STABLE PRODUCTION AND GOOD QUALITY
The Cell Line Development group is focused on the development of novel platform technologies for rapid generation of cell lines producing high titer and good quality therapeutic antibodies to meet the industrial needs. Chinese hamster ovary (CHO) cells are the dominant host for producing therapeutic antibodies because of their capacity to perform proper folding, assembly and post-translational modifications. Developing CHO production cell lines is the first step of antibody manufacturing which determines not only the cost-of-goods but also the efficacy and toxicity of drug substances. Cell line development is also the bridge from the antibody development to clinical trials. Our group has developed a CHO targeted integration platform which allows generation of CHO production cell lines with antibody titer ranging from 2 to 5 g/L in typical fed-batch cultures. Leveraging capabilities in analytics and process development within BTI, we are able to develop and characterize production clones for optimal cell-metabolic features and product quality, manufacturability, and stability before Master Cell Bank (MCB) decision.
Our group also directs effort toward engineering CHO cells for producing other high value materials, such as heparan sulfate (HS). HS are ubiquitous glycan molecules present on many cell types. Many therapeutically relevant proteins must be bound to HS to properly function. Potential applications of HS include binding of growth factors for enhancing growth of hMSC in culture and wound healing, coating for medical devices to increase blood compatibility and inhibitors for viral invasion such as in the case of COVID-19. As the majority of HS/ heparin is animal-derived, the safety and supply of raw materials are under scrutiny due to adulteration incidents and inconsistency in supply. Leveraging in our CHO targeted integration platform and genetic tools for precisely controlling expression level of multiple genes, we are engineering the entire HS synthesis pathway in CHO cells with the aim of producing various HS structures to address different applications.