NSF CMaT Researchers Assess T Cell Quality Using Patient-Specific Potency Chips
Outcome/Accomplishment
Researchers at the National Science Foundation (NSF)-funded Engineering Research Center (NSF ERC) for Cell Manufacturing Technologies (NSF CMaT) are using 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 common form of brain cancer. The researchers have designed a novel cell-intrinsic strategy to genetically reprogram primary human T cells to autonomously detect and eliminate dysfunctional cells. The NSF CMAT ERC is headquartered at the Georgia Institute of Technology (Georgia Tech).
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 provides for the first time 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-a-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-a-chip platform revealed CAR T efficacy or toxicity (E:T)-dependent cell 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-a-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). KLRC1 binds to human leukocyte antigen E (HLA-E) molecules to help control immune system activity and prevent healthy cells from being attacked. The research team achieved 98% KLRC1 knock-out efficiency and 23% knock-in efficiency of GD2 CAR transgene using a single-step virus-free gene editing method. A cone-based Ieukocyte reduction system (LRS) isolation method was improved to significantly enhance CAR-NK cell viability. The research team was also able to integrate a high-efficiency viral transduction platform into a closed-loop vertical wheel bioreactor system that reduces viral vector usage by two to tenfold.
This work has resulted in eight papers, seven conference presentations, and three filed patents for the research team led by Lohitash Karumbaiah at the University of Georgia, a CMaT core partner institution.
Location
Atlanta, GeorgiaStart Year
Advanced Manufacturing
Advanced Manufacturing
Lead Institution
Core Partners
Fact Sheet
Outcome/Accomplishment
Researchers at the National Science Foundation (NSF)-funded Engineering Research Center (NSF ERC) for Cell Manufacturing Technologies (NSF CMaT) are using 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 common form of brain cancer. The researchers have designed a novel cell-intrinsic strategy to genetically reprogram primary human T cells to autonomously detect and eliminate dysfunctional cells. The NSF CMAT ERC is headquartered at the Georgia Institute of Technology (Georgia Tech).
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 provides for the first time 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-a-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-a-chip platform revealed CAR T efficacy or toxicity (E:T)-dependent cell 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-a-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). KLRC1 binds to human leukocyte antigen E (HLA-E) molecules to help control immune system activity and prevent healthy cells from being attacked. The research team achieved 98% KLRC1 knock-out efficiency and 23% knock-in efficiency of GD2 CAR transgene using a single-step virus-free gene editing method. A cone-based Ieukocyte reduction system (LRS) isolation method was improved to significantly enhance CAR-NK cell viability. The research team was also able to integrate a high-efficiency viral transduction platform into a closed-loop vertical wheel bioreactor system that reduces viral vector usage by two to tenfold.
This work has resulted in eight papers, seven conference presentations, and three filed patents for the research team led by Lohitash Karumbaiah at the University of Georgia, a CMaT core partner institution.