Cell-based therapies for cancer treatment: leveraging advanced flow cytometry for greater clinical insight

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Recent advances have revolutionized cancer treatment by specifically targeting and destroying cancerous cells via the body’s own immune system, giving rise to the rapidly expanding field of immuno-oncology. These novel treatments are diverse in origin, spanning from antibody-based therapies such as checkpoint inhibitors to adoptive cell therapies, including CAR-T and CAR-NK cells. While immuno-oncology treatments can be highly effective, several challenges limit the implementation of these new therapies. For example, not all patients respond robustly to immune-based treatments and it is difficult to predict which patients are likely to benefit from treatment.

Additional hurdles include the high cost and technical difficulties associated with purifying, phenotyping and expanding immune cells from patients. This is due in part to the limitations of traditional cell and secreted protein analysis methods that are low-throughput or lack the ability to capture dynamic immune cell data. There exists a need to use innovative tools to link insights from both immune cell health, proliferation and phenotype as well as cytokine secretion profiles. Moving towards high throughput, multiplexed and streamlined tools, such as advanced flow cytometry, to study immune cell response, can overcome bottlenecks compared to traditional methods and further the development and use of novel cancer therapies.

Discussion on the overall importance and development of therapeutic antibodies
The practical advantages of advanced flow cytometry over traditional methods, to purify and phenotype patient immune cells
How advanced flow cytometry may be used to streamline the development of CAR-T and CAR-NK cells.

Nina Senutovitch Ph.D.

Senior Scientist, Product Development, Cell Imaging, Sartorius

Dr. Nina Senutovitch received her BS in Biochemistry from New Mexico State University. She completed her PhD in Biological Sciences from Carnegie Mellon University, where she developed and detailed the function of novel fluorescent probes. As a post-doctoral fellow at the University of Pittsburgh, she established biosensor-based live cell screening assays for the detection of hepatotoxicity, including the use of a human liver “organ on a chip” model. She joined Sartorius in 2019 as a Senior Scientist in Cell Analytics.

Rong Fan Ph.D

Professor of Biomedical Engineering, Yale University

Dr. Rong Fan is Professor of Biomedical Engineering at Yale University. His research interest has been centered on the development and deployment of single-cell omics and high-resolution spatial omics technologies to investigate complex human diseases. He received a B.S. in Applied Chemistry from University of Science and Technology of China, a Ph.D. in Chemistry from the University of California at Berkeley, and then completed his postdoctoral training at California Institute of Technology, prior to joining the faculty of Department of Biomedical Engineering at Yale University in 2010. He developed a microchip that allows for simultaneous measurement of 42 immune effector proteins in single cells at high throughput, which remains the highest multiplexing to date for a single-cell protein secretion assay. In collaboration with Novartis and Kite Pharma, it was applied to profiling antigen-specific activation states of chimeric antigen receptor (CAR)-engineered T cells, resulting in the discovery of novel single-cell biomarkers including polyfunctional strength index to characterize the quality of CAR-T infusion products and predict the clinical responses and immune-related adverse effects(irAEs) prior to treatment. This microchip, called IsoCode, and the automation system, called IsoLight, have been commercialized by IsoPlexis, a company co-founded by Dr. Fan. Now, this system has been used by >100 major pharmaceutical companies and cancer centers around the world for monitoring CAR-T or checkpoint inhibitor immunotherapies. In addition, Dr. Fan is also working to develop high-throughput methods for single-cell epigenomic, transcriptomic, and epi-transcriptomics such as microRNAs. Recently, his laboratory developed the first high-spatial-resolution spatial multi-omics sequencing technology (Liu et al., 2020, Cell 183, 1665–1681) which may find widespread applications in developmental biology, neuroscience, cancer research, immunobiology and clinical pathology. Dr. Fan co-founded IsoPlexis, Singleron Bio, and AtlasXomics. He is the recipient of multiple awards including the NCI Howard Temin Career Transition Award, the NSF CAREER Award, and the Packard Fellowship for Science and Engineering. He is elected a Fellow of American Institute for Medical and Biological Engineering (AIMBE) and a Senior Member of National Academy of Inventors (NAI).

Tamara J. Laskowski, Ph.D.

Scientific Project Director, Adoptive Cell Therapy Platform, Dept. of Stem Cell Transplantation and Cellular Therapy MD Anderson Cancer Center

Having originally joined Dr. Laurence J.N. Cooper’s laboratory as a fellow, where her work focused on engineering stem cells with the goal of generating off-the-shelf NK and T-cell immunotherapies for targeting solid tumor malignancies, Dr Tamara Laskowski recently transitioned to Dr. James Allison’s Immunotherapy Platform at MD Anderson Cancer Center. In her new role Dr. Laskowski’s work primarily involves immune-monitoring of patients undergoing clinical trials in Immunotherapy and development of novel immunoassays.

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