Cell therapies, such as CAR-T cells, are increasingly important for the treatment of cancer and other maladies. Production of such therapies involves a series of time-intensive steps that have been translated from cell biology laboratory-based procedures. This proposal aims to produce innovative modular technologies for the production of cell therapies with improved scalability and enhanced consistency and efficacy.
The University of Delaware and team aim to develop innovative modular technologies to produce cell therapies with improved scalability, enhanced consistency and efficacy, and the potential for reduced cost.
A prototype technology recently was established that integrates scalable, functionalized soft membranes into a flow-based device for enhancing T cell transduction and promoting T cell activation (completed PC3.1-132).
This work (PC5.2T-108) will build from this successful prototype to address more processing steps and other cell therapies, facilitated by the growth of our academic-industrial partnerships.
Demonstrate devices for longer-term T-cell processing steps including closed-loop phenotype selection, activation, expansion, and transduction.
Establish workflows for enhancing the transduction of difficult-to-transduce cell types
Establish functionalities and workflows for cost-effective, short-term rapid T-cell processing steps.
By transitioning from manual, lab-based procedures to an integrated flow-based device, this project aims to reduce the current 14–21 day CAR-T production cycle by an estimated 30% to 50%. The use of functionalized soft membranes enhances transduction efficiency and scalability, directly targeting a significant reduction in the $300,000+ per-patient manufacturing cost of cell therapies. Furthermore, this modular technology improves consistency across difficult-to-transduce primary cells, such as NK cells and macrophages, ensuring higher product potency and reduced waste during the complex expansion phase.
Deliverable: single device optimized for modular transduction demonstrating improved transduction over static conditions Device operating conditions have been demonstrated that give statistically similar or enhanced (up to 5-fold) transduction of primary T cells relative to static culture depending on the lentivirus used. Processing steps are now being combined (e.g., selection + transduction, activation + transduction), where transduction enhancement of primary T cells with CD19 has been demonstrated in the device with CD8 selection + CD19 transduction. Successful operating conditions have been identified for CD8+ or CD4+ Selection to produce an enriched population (>80% positive selection of target population). Sequential process established with activation, transduction, and expansion for production of efficacious CAR T product.
Kloxin, A., Conference Participant, 5.2T-108 Innovative scalable technologies for production of cell therapies, NIIMBL National Meeting, Washington, D.C., June 26, 2025.
Lopez Ruiz, A., Slaughter, E., LeValley, P., Bomb, K., Yun, Z., McCoskey, J., Levine, K., Chatterjee, A., Carbrello, C., Chang, D., Abassi, Y., Lenhoff, A., Fromen, C. A., & Kloxin, A., Flow-based membrane technology to engineer T-cells, ECI Advancing Manufacture of Cell and Gene Therapies VIII, Coronado, CA, February 4, 2024.
Kloxin, A., Speaker, Photopolymerizations for creating engineered microenvironments: From 3D culture models to biomanufacturing, Boulder, CO, Sept 19-22, 2024.
Lopez Ruiz, A., Bomb, K., Slaughter, E., LeValley, P., Yun, Z., McCoskey, J., Levine, K., Chatterjee, A., Carbrello, C., Chang, D., Abassi, Y., Lenhoff, A., Fromen, C. A., & Kloxin, A., Flow-based membrane technology to engineer T-cells, Controlled Release Society, Las Vegas, NV, July 25, 2023.
Lopez Ruiz, A., Slaughter, E., Yun, Z., Bomb, K., Carbrello, C., Lenhoff, A., McCoskey, J., Levine, K., LeValley, P., Fromen, C. A., & Kloxin, A., Flow-Based Membrane Technology to Engineer T-Cells, American Institute of Chemical Engineers 2023 National Meeting, Orlando, Florida, November 5, 2023. https://aiche.confex.com/aiche/2023/meetingapp.cgi/Paper/670238
Login to the NIIMBL member portal to access additional project information, including presentations, progress updates, reports, and more.
Not yet a member? Learn more about which level of NIIMBL membership is right for you and your organization.
University of Delaware
Agilent
EMD Millipore Corporation
