Lack of appropriate biophysical cues within commercial activation reagents and processes increases the risk of generating suboptimal cell populations, which can have implications for inefficient cell activation, higher cost of treatment, increased vein-to-vein time, and reduced functionality of cells in vivo.
Create a single, modular, and scalable platform capable of both biophysical and flow enhancements for promoting the activation, proliferation, and transduction of T-cells, with opportunities for selection and integration.
Develop an innovative technology platform for cell therapy manufacturing that can accommodate all the necessary unit operations, including separation of cell phenotypes, activation and transduction, and expansion of purified phenotypes
Integration of tailorable soft materials that will provide optimal microenvironments to facilitate and control cell capture, release, manipulation, and promotion of desired functions
By implementing a modular, functionalized hydrogel-coated membrane (HCM) system integrated with tangential flow filtration (TFF), an organization will reduce T-cell activation and transduction time by up to 30–50% and improve transduction efficiency several-fold, enabling scalable, flexible biomanufacturing of adoptive T-cell therapies
Synthesize hydrogel coated membrane (HCM) and functionalize with ATCT-stimulating antibodies to control surface mechanical and biochemical properties in TFF device Assess enhancements from HCM-TFF prototype in ATCT transfection and activation Assemble and operate HCM-TFF device at partner laboratories, as well as pilot use for selection
Bomb, K., LeValley, P. J., Woodward, I. R., Cassel, S. E., Sutherland, B. P., Bhattacharjee, A., Yun, Z., Steen, J., Kurdzo, E., McCoskey, J., Burris, D., Levine, K., Carbrello, C., Lenhoff, A. M., Fromen, C. A., & Kloxin, A. M. (2023). Cell Therapy Biomanufacturing: Integrating Biomaterial and Flow-Based Membrane Technologies for Production of Engineered T-Cells. Advanced Materials Technologies, 8(6). https://doi.org/10.1002/admt.202201155
Lopez Ruiz, A., Slaughter, E. D., Kloxin, A. M., & Fromen, C. A. (2024). Bridging the gender gap in autoimmunity with T-cell-targeted biomaterials. Current Opinion in Biotechnology, 86. https://doi.org/10.1016/j.copbio.2024.103075
Bomb, K., LeValley, P., Sutherland, B., Steen, J., Du, Z., Carbrello, C., Kloss, C., Lenhoff, A., Fromen, C. A., & Kloxin, A., Combining flow-based membrane and tunable biomaterial technologies to improve the scalability and efficiency of biomanufacturing approaches for cell therapies, 2021 Merck Emerging Talent Symposium, Virtual, November 4, 2021.
Kloxin, A., Presenter, PC3.1-132 Improving biomanufacturing of T cell therapies using tunable biomaterials and flow-based membrane technologies, NIIMBL National Meeting, Washington, D.C., July 27, 2022.
Bomb, K., LeValley, P., Woodward, I., Yun, Z., Sutherland, B., Cassel, S., Kurdzo, E., McCoskey, J., Du, Z., Levine, K., Carbrello, C., Lenhoff, A., Fromen, C. A., & Kloxin, A., Improving biomanufacturing of T cell therapies using tunable biomaterials and flow-based membrane technologies, NIIMBL National Conference, Washington, DC, July 26, 2022.
Bomb, K., LeValley, P., Woodward, I., Yun, Z., Sutherland, B., Cassel, S., Kurdzo, E., McCoskey, J., Levine, K., Carbrello, C., Lenhoff, A., Fromen, C. A., & Kloxin, A., Combining tunable biomaterials and flow-based membrane technologies for improved biomanufacturing of T cell therapies, American Institute of Chemical Engineers Annual Meeting, Phoenix, AZ, November 13, 2022.
Cell separation, processing, and expansion for cell therapy applications (PC3.1-132), NIIMBL Member Forum, Virtual, November 18, 2021.
LeValley, P., Bomb, K., Sutherland, B., Steen, J., Kurdzo, E, Du, Z., Carbarello, C., Lenhoff, A., Fromen, C., & Kloxin, A., Combining flow-based membrane and tunable biomaterial technologies to improve the scalability and efficiency of biomanufacturing approaches for cell therapies, American Chemical Society (ACS) Fall 2021 National Meeting, Atlanta, GA, August 25, 2021.
LeValley, P., Bomb, K., Sutherland, B., Steen, J., Kurdzo, E., Du, Z., Carbrello, C., Lenhoff, A., Fromen, C. A., & Kloxin, A., Cell separation, processing, and expansion for cell therapy applications, NIIMBL National Meeting, Virtual, July 15, 2021.
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
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University of Delaware
EMD Millipore Corporation
Merck Sharp & Dohme LLC
