The Switzerland-headquartered contract development and manufacturing organization (CDMO) developed its Cocoon platform to address the "inefficiencies" of manufacturing cell and gene therapies (CGTs). It was launched commercially about 18 months ago.
Now, in order to tackle challenges of variability in starting material, the platform has newly added ‘magnetic cell selection’ capabilities, which can be utilized at any point in the cell therapy manufacturing process, and are designed to provide a high level of customization and consistency, said Lonza
Magnetic cell separation is an established technique allowing for the selection and enrichment of specific cell types from cell suspensions and complex matrices, it added.
“The magnetic selection on the Cocoon Platform is a vital new addition to manufacturing for cell therapies, and Lonza’s clients are currently utilizing the new capabilities to advance new techniques. Several of these efforts are underway globally, and some clients have reported early results on these efforts,” commented Tamara Laskowski, head of clinical development, personalized medicine, Lonza.
Issues around starting material
When manufacturing CGTs, a significant challenge is the consistency and quality of cell therapy products due to the product complexity and patient-specific variability. In addition, the quality of fresh and frozen starting material influences the end-product, said the CDMO.
Laskowski told us how the expanded functionality addresses such challenges.
“The fundamental principle underlying magnetic selection consists of targeting specific cell types, which are then bound to antibodies cross-linked to magnetic particles. Cells labeled with magnetic particles can be retained when placed within a magnetic field while non-labeled cells are free to flow through. The ability to efficiently select the cells of interest allows for uniformization of the starting material, thereby minimizing inter-patient/inter-donor variability that may impact downstream manufacturing applications.
“By ensuring the starting population is enriched for T cells, for instance, one can more accurately monitor critical process parameters such as initial T cell seeding number, the concentration of T cell activating agent, virus multiplicity of infection (MOI), and cell proliferation. Furthermore, the selection process also helps to remove other cell types, such as monocytes, which can interfere with early-process activities and may be present in patient or donor samples at varying frequencies.”
The new magnetic cell selection capability is implemented and carried out directly into the same, singular consumable cassette that is used for the duration of the manufacturing process. "The Cocoon Platform only requires the use of antibodies and magnetic reagents to target the desired purification strategy.”
In the platform, the magnetic array is located within the environmental unit, behind the base plate and is only engaged during selection activities, continued the Lonza representative. The rear of the cassette contains a corresponding pathway of tubing that is directly adjacent to the magnetic array and provides a reusable fluidic path where labeled cells are retained.
“This solution offers additional flexibility and customization potential and is appropriate for positive, negative and sequential magnetic separation. If required, bead removal can also be performed in an automated fashion, taking place within the same cassette. This innovative design allows for selection at any point in the process while also enabling the other unit operations traditionally associated with cellular manufacturing, such as sample acquisition, activation, transduction/transfection, expansion, and formulation, which can be tailored by users for their specific process needs,” said Laskowski.
Driving down manufacturing costs
Looking at the impact the platform has made on the industry since its launch, she has seen "tremendous interest" in the closed system from all sectors of the cell therapy field. "Our early adopters from academia, biotech, and contract manufacturing organizations (CMOs) have provided important feedback that we have used to continually improve the platform processes and guide the design and implementation of future functionality.”
She said the widespread embrace of the platform globally speaks to the limited number of options for such "easy-to-operate, all-in-one, automated" systems.
“The plug-and-play nature of the consumable cassette and flexible programming modes to support a variety of reagents have demonstrated that the Cocoon Platform can meet the current needs of the field. Moreover, along with the Cocoon Tree, the Cocoon Platform is designed to address the challenges around efficiently scaling these therapies. By utilizing the vertical space of cleanrooms more effectively, we will drive down the manufacturing costs and improve patient access to these therapies.”