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Challenges remain in cell therapy manufacturing optimization and scalability, especially when developing autologous therapies. In a recent GEN webinar, Matthew Hewitt, PhD, head of R&D (a.i.) and clinical development, personalized medicine at Lonza, and Stacey Willard, PhD, director of product management at IsoPlexis, provided an overview of the Cocoon™ cell therapy manufacturing platform and the IsoLight™ single-cell proteomics system along with data from case studies.
These next-generation technologies allow for the decentralized manufacturing of novel cell therapies and the complete functional characterization of each single cell in the resultant product. The combination improves end-to-end automation by minimizing the need for human involvement and helps ensure functional potency of the manufactured cell products. To view the on-demand webinar, visit GENengnews.com/IsoLight.
Each cell therapy approach has intricacies. The automated cell therapy manufacturing Cocoon platform is designed to alleviate pain points for patient-scale production. The closed, scalable platform uses a single-use customizable cassette that can accommodate a variety of cell therapy processes.
The environmental shell, cassette, and software are the Cocoon’s three main units. The dual-zone environmental unit offers a 37°C warm temperature proliferation zone for the cells and a 4°C refrigerated zone for reagents and waste. The intuitive software is 21 CFR Part 11 compliant and supports quick process modification. The scalable Cocoon tree has a small footprint and allows use of up to eight cassettes for simultaneous clinical trials or commercial production.
To demonstrate the capabilities of the Cocoon system, Hewitt presented a comparison study with a culture bag system for a HER2 lentiviral vector CAR-T process. Results showed higher viability in the Cocoon system as well as an increase in transduction efficiency and the number of transduced cells. Transduced cells expressed similar IFNγ and TNFα, and were comparable in co-culture tumor killing assays.
Combining the IsoLight system with the Cocoon platform allows quantification of the true functional biology of the cell product. Although other analytic approaches provide rich data, they do not reveal single cell functional detail, which facilitates better predictions of potency, durability, and adverse effects.
The IsoLight’s functional phenotyping is emerging as the “standard biomarker” in immune medicine, the only functional cellular analysis tool that can uniquely detect predictive “high-functional” super cells to uncover cellular signals or correlative biomarkers.
The automated IsoLight system is an integrated “plug & play” hardware and software solution for all IsoPlexis chip products. Willard detailed how the proteomically barcoded chip enables quantification of 30+ proteins simultaneously per cell providing useful, impactful single cell data. Panels exist to measure the secretome, proteome, and metablome.
The software quickly generates great visualizations to stratify samples, reveal functional differences, pinpoint biological drivers, and calculate the significance of the polyfunctionality of the cells.
IsoPlexis has been involved in the creation of many durable potent cell therapy products, using a wide variety of cell types. This single cell analysis fits into the manufacturing process at any and all stages, and is critical to gaining an understanding of the true function of the cells that can be masked at the population level.
IsoPlexis’ single-cell proteomics and quality analytics are applicable at every stage of development from preclinical mouse research, process development, all the way to patient characterization and stratification. To demonstrate the importance of this metric, Willard illustrated data from several recent publications.
For example, collaboration with Kite Pharma on their CD19 CAR-T product showed a correlation between polyfunctionality and treatment response. In other studies, the predictive polyfunctionality enhanced cell therapy development, and was correlated with preclinical outcome in gene-edited therapies, novel CAR-T comparisons, and combination T-cell therapies and agonists.
“This collaboration between Lonza and IsoPlexis highlights the evolution of cell therapy manufacturing. As we continue to scale the manufacturing of cell therapies, it will be critical to characterize the quality and performance of these products with technologies such as IsoPlexis’ IsoLight,” said Hewitt.