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A Killer Strategy: Monitoring Engineered Immune Cell Prowess

Washington University School of Medicine

4-December-20

 

Dr. Carl DeSelm is an assistant professor of radiation oncology in the Bursky Center for Human Immunotherapy and Immunology Programs (CHiiPs) at Washington University School of Medicine in St. Louis, Missouri.  Dr. DeSelm also has a radiation oncology practice at the Siteman Cancer Center at Barnes-Jewish Hospital. Industry recognitions for his research and clinical accomplishments span far and wide, including the 2020 Agilent Early Career Professor Award.

A central focus of Dr. DeSelm’s research is to help overcome the challenges and improve immune cell engineering related to the development of chimeric antigen receptor (CAR) T cell therapies. CAR T cell therapies, wherein ex vivo T cells are specially trained to find and destroy tumor cells, hold significant promise as a cancer treatment pillar.  The concept seems simple enough, yet the challenge lies in its implementation - CAR T cells may be limited in recognizing target molecules on tumor cells, especially if the tumor cells mount a defense mechanism such as antigen escape. On top of that, the target molecules must be expressed by all targeted tumor cells but not expressed by healthy cells. In a solid tumor, it may be difficult for the CAR T cells to penetrate the three-dimensional structure.

Fluorescence and brightfield imaging, along with video creation, are critical methods used in Dr. DeSelm’s research into immune functions and effectiveness. For these tasks, his team relies on the BioTek Cytation 5 cell imaging multimode reader. He recalls that his lab team was initially looking for ways to reliably measure immune-mediated phagocytosis of tumor cells over time, and Cytation 5 provided quantified data that was reflective of the gold standard fluorescence-assisted cell sorting (FACS) assays. “With Cytation 5, we can video the entire process of a macrophage phagocytosing a live tumor, which is a rare event,” he explains of the switch to the new instrument. “We don’t have to worry about data irregularity caused by cells sticking together or a macrophage taking up dead tumor cell.”

Cytation 5 has also opened the door to other applications in Dr. DeSelm’s laboratory. “Everyone in the lab is enthusiastic about the large number of assays, including long-term experiments that they can perform in 6- to 384-well microplate formats using Cytation 5” Dr. DeSelm summarizes. “It’s central to much of our research, and the fact that it can assay a large number of samples in a blinded, quantitative and consistent manner gives us confidence in the robustness of our findings.”

Imaging macrophage-tumor

Imaging macrophage-tumor interactions using Cytation 5. Macrophages (red) and tumor cells (green) incubated with various immune modulators (here, CpG) are monitored over time, and cell death is visualized with DAPI (blue). Image copyright of Washington University School of Medicine St. Louis.


Learn more about Dr. DeSelm’s research by visiting the laboratory’s website.  

 

 

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Washington University in St. Louis



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