NSF CMaT Researchers Develop Patient-Specific Potency Chips to Assess T Cell Quality
Outcome/Accomplishment
Researchers at the Engineering Research Center (ERC) for Cell Manufacturing Technologies (CMaT) have successfully developed multi-niche human Multiple Myeloma (MM) and Glioblastoma (GBM) potency chips to assess T cell quality. Multiple myeloma is a type of cancer that affects plasma cells, which are white blood cells that produce antibodies. Glioblastoma is a highly aggressive and most common form of brain cancer. The NSF CMAT ERC is funded by the National Science Foundation (NSF) and headquartered at the Georgia Institute for Technology and the University of Georgia.
Impact/Benefits
T cells are a type of white blood cell and lymphocyte that are crucial for cell-mediated immunity, a part of the immune system that directly fights pathogens and abnormal cells. Patient-specific potency chips—like those developed by NSF CMaT—are also known as microfluidic chips or "organ-on-a-chip" platforms. They can be used to assess T-cell quality by recreating a personalized tumor microenvironment in vitro. These advanced systems analyze individual T-cell characteristics, behavior, and killing efficacy against a patient's own cancer cells to predict immunotherapy response. This work overcomes the absence of physiologically relevant potency assay platforms for testing the effectiveness of manufactured CAR T and natural killer (NK) cells for MM and GBM.
Explanation/Background
Georgia Tech’s new microfluidic platform successfully demonstrates a significantly higher correlation between the human mesenchymal stromal cells (MSC) secretory response within the microfluidic assay and the MSC response in vivo compared to traditional 2D cultures. The MM-on-chip platform encapsulates and preserves the necessary cell types for killing target cells. It has been used to validate clinical samples and will be commercialized by a startup company, Cellcue Bio, for CAR-T potency testing, an evaluation of the functional capacity of engineered T cells necessary for regulatory compliance. Cellcue Bio engineers on-chip platforms for robust, high-throughput, predictive cell potency metrics. The team is currently evaluating cytolytic activity for other CAR-T cells as well as secreted cytokines which may provide additional potency metrics.
The GBM-on-chip platform revealed CAR T efficacy or toxicity (E:T) dependent killing. Potency testing of multiple CAR T cell products against different patient-derived GBM neurospheroids revealed CAR T cell E:T dependent killing of different patient derived GBM neurospheroids. It is being used for characterizing thermos-responsive terpolymer hydrogels. The research team found that continuous, label-free quantitative oblique back-illumination microscopy (qOBM) imaging on chip correlates strongly with flow cytometry measurements of cell viability.
These platforms can also be adapted for other metastatic cancers and immunotherapies (e.g., NK cell therapies). The work resulted in four publications and five conference presentations for the research team led by Lohitash Karumbaiah at the University of Georgia.
Publications:
https://doi.org/10.1002/jbm.a.37823
https://onlinelibrary.wiley.com/doi/10.1002/jbm.a.37823
https://opg.optica.org/abstract.cfm?uri=Microscopy-2024-MM5A.4
Conference Publications:
1. Davarzani A., Tondepu C., Zhao L., Mamaghani D., Liu Y., Mao L., Karumbaiah L., Characterization of a Tumor-on-Chip Platform for Replicating the Glioblastoma Microenvironment. SLAS 2024 Building Biology in 3D, West Palm Beach, FL, April 2024.
2. Filan, C., Davarzani, A., Cappabianca, D., Tommasi, A., Sarko, L., Denne, N. L. V., ... & Robles, F. E., Three-dimensional Quantitative Phase Imaging for the Assessment of Glioblastoma Multiforme Treatment Efficacy in Human Spheroids. Microscopy Histopathology and Analytics, Optica Publishing Group, Fort Lauderdale, FL, April 2024.
3. Davarzani A., Speier L., Tondepu C., Patel K., Mao L., Karumbaiah L., Therapeutic potency testing of drug-loaded microparticles against glioblastoma using a perfusable tumor-on-chip platform. BMES 2023, Seattle, WA, Oct 2023.
4. Slusher, G., Kottke, P., Fedorov, A, A Microfluidic Platform for Extracellular Vesicle Sorting and Inline ESI-MS Analysis for Cell Therapy Biomanufacturing. 72nd American Society for Mass Spectrometry (ASMS) Conference on Mass Spectrometry and Allied Topics, Anaheim, CA, June 2024.
5. Fedorov A. G., MicroTAS (Total Analysis System) for Dynamic ESI-MS Monitoring of Extracellular Proteome and Intracellular Metabolome in Cell and Gene Therapy Biomanufacturing, 25th International Mass Spectrometry Conference, Melbourne, Australia, August 17-23, 2024.
Location
Atlanta, GeorgiaStart Year
Advanced Manufacturing
Advanced Manufacturing
Lead Institution
Core Partners
Fact Sheet
Outcome/Accomplishment
Researchers at the Engineering Research Center (ERC) for Cell Manufacturing Technologies (CMaT) have successfully developed multi-niche human Multiple Myeloma (MM) and Glioblastoma (GBM) potency chips to assess T cell quality. Multiple myeloma is a type of cancer that affects plasma cells, which are white blood cells that produce antibodies. Glioblastoma is a highly aggressive and most common form of brain cancer. The NSF CMAT ERC is funded by the National Science Foundation (NSF) and headquartered at the Georgia Institute for Technology and the University of Georgia.
Location
Atlanta, GeorgiaStart Year
Advanced Manufacturing
Advanced Manufacturing
Lead Institution
Core Partners
Fact Sheet
Impact/benefits
T cells are a type of white blood cell and lymphocyte that are crucial for cell-mediated immunity, a part of the immune system that directly fights pathogens and abnormal cells. Patient-specific potency chips—like those developed by NSF CMaT—are also known as microfluidic chips or "organ-on-a-chip" platforms. They can be used to assess T-cell quality by recreating a personalized tumor microenvironment in vitro. These advanced systems analyze individual T-cell characteristics, behavior, and killing efficacy against a patient's own cancer cells to predict immunotherapy response. This work overcomes the absence of physiologically relevant potency assay platforms for testing the effectiveness of manufactured CAR T and natural killer (NK) cells for MM and GBM.
Explanation/Background
Georgia Tech’s new microfluidic platform successfully demonstrates a significantly higher correlation between the human mesenchymal stromal cells (MSC) secretory response within the microfluidic assay and the MSC response in vivo compared to traditional 2D cultures. The MM-on-chip platform encapsulates and preserves the necessary cell types for killing target cells. It has been used to validate clinical samples and will be commercialized by a startup company, Cellcue Bio, for CAR-T potency testing, an evaluation of the functional capacity of engineered T cells necessary for regulatory compliance. Cellcue Bio engineers on-chip platforms for robust, high-throughput, predictive cell potency metrics. The team is currently evaluating cytolytic activity for other CAR-T cells as well as secreted cytokines which may provide additional potency metrics.
The GBM-on-chip platform revealed CAR T efficacy or toxicity (E:T) dependent killing. Potency testing of multiple CAR T cell products against different patient-derived GBM neurospheroids revealed CAR T cell E:T dependent killing of different patient derived GBM neurospheroids. It is being used for characterizing thermos-responsive terpolymer hydrogels. The research team found that continuous, label-free quantitative oblique back-illumination microscopy (qOBM) imaging on chip correlates strongly with flow cytometry measurements of cell viability.
These platforms can also be adapted for other metastatic cancers and immunotherapies (e.g., NK cell therapies). The work resulted in four publications and five conference presentations for the research team led by Lohitash Karumbaiah at the University of Georgia.
Publications:
https://doi.org/10.1002/jbm.a.37823
https://onlinelibrary.wiley.com/doi/10.1002/jbm.a.37823
https://opg.optica.org/abstract.cfm?uri=Microscopy-2024-MM5A.4
Conference Publications:
1. Davarzani A., Tondepu C., Zhao L., Mamaghani D., Liu Y., Mao L., Karumbaiah L., Characterization of a Tumor-on-Chip Platform for Replicating the Glioblastoma Microenvironment. SLAS 2024 Building Biology in 3D, West Palm Beach, FL, April 2024.
2. Filan, C., Davarzani, A., Cappabianca, D., Tommasi, A., Sarko, L., Denne, N. L. V., ... & Robles, F. E., Three-dimensional Quantitative Phase Imaging for the Assessment of Glioblastoma Multiforme Treatment Efficacy in Human Spheroids. Microscopy Histopathology and Analytics, Optica Publishing Group, Fort Lauderdale, FL, April 2024.
3. Davarzani A., Speier L., Tondepu C., Patel K., Mao L., Karumbaiah L., Therapeutic potency testing of drug-loaded microparticles against glioblastoma using a perfusable tumor-on-chip platform. BMES 2023, Seattle, WA, Oct 2023.
4. Slusher, G., Kottke, P., Fedorov, A, A Microfluidic Platform for Extracellular Vesicle Sorting and Inline ESI-MS Analysis for Cell Therapy Biomanufacturing. 72nd American Society for Mass Spectrometry (ASMS) Conference on Mass Spectrometry and Allied Topics, Anaheim, CA, June 2024.
5. Fedorov A. G., MicroTAS (Total Analysis System) for Dynamic ESI-MS Monitoring of Extracellular Proteome and Intracellular Metabolome in Cell and Gene Therapy Biomanufacturing, 25th International Mass Spectrometry Conference, Melbourne, Australia, August 17-23, 2024.