ACEA Biosciences Inc.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly utilized in basic biology research, drug discovery applications, and for studies of disease mechanisms. The opportunity to measure the contractility, viability, and electrophysiology of hiPSC-CMs in real time over extended periods can provide researchers unique mechanistic insights into the roles cardiomyocytes play in both normal development and cardiac disease.

In this special webinar, scientists using hiPSC-CMs will describe new approaches aimed at enhancing assessment of hiPSC-CM functionality. The speakers will also discuss how these approaches can be used to explore compounds that modulate the force of cardiomyocyte contraction or to assess the safety and efficacy of drugs and drug combinations targeting cardiac tissue.

In this webinar, you will gain insights on:

• New instrumentation to assess cardiomyocyte contractility, viability, and electrophysiology
• Label-free, real-time techniques to assess the “beating” of cardiomyocytes as a biologically-relevant measure of cardiomyocyte function
• Use of electrical pacing for further maturation of cardiomyocytes
• Techniques to detect functional cardiotoxicity

In addition, you will also be able to ask your own specific questions of the speakers during a live question-and-answer session following the presentations.

Featured Speaker:

Armando Lagrutta, PhD
Merck & Co. Inc.
Kristina Green, PhD
MyoKardia, Inc.

Moderator:

Patrick C.H. Lo, PhD
Senior Editor,
BioTechniques

Featured Speaker:

Dan MacLeod Ph.D.
Precision BioSciences, Inc.

Dr. MacLeod received his Ph.D. in Molecular Pathology and Biomedical Sciences from the University of California, San Diego (UCSD). He subsequently conducted postdoctoral research at the International AIDS Vaccine Initiative Neutralizing Antibody Center at the Scripps Research Institute. Dr. MacLeod is currently leading a group in Precision BioScience’s Cell Therapy Research team, focused on expanding the use of Precision’s propriety ARCUS gene-editing technology to engineer T cells for cancer therapy.

Abstract: 

Adoptive cellular therapy using chimeric antigen receptor (CAR) T cells has produced significant responses in patients with CD19+ hematological malignancies. Most clinical trials to date have used autologous patient cells, which incur significant manufacturing challenges and costs and are not feasible for many patients with advanced disease state.

At Precision BioSciences, we have developed an allogeneic method using our proprietary ARCUS™ gene-editing technology to generate “universal” CAR T cells from healthy donors. These cells are engineered to eliminate expression of the endogenous T cell receptor making them safe for transfer to unrelated patients. By integrating the CAR transgene at a single genomic site, we can tightly control the level of CAR expression on the cell surface. We further optimize the cells by designing new CAR T constructs that include modifications to the extracellular binding domains as well as the intracellular signaling domains.

Evaluating the impact of these new modifications requires sensitive methods to assay CAR T cell function. Traditional methods for evaluating cytotoxicity cannot effectively predict in vivo activity of a CAR T product; this is because they assess short-term killing potential rather than the ability to expand, persist, and exhibit serial killing. We have used the ACEA xCELLigence instrument for both B Cell Killing Assays and Leukemic Cell Killing Assays to test multiple CAR constructs with modified ectodomains, endodomains, and other modifications, and we have found this platform sensitive enough to detect subtle yet significant differences in performance not observed in traditional killing assays. Furthermore, the sensitivity of the instrument has enabled us to evaluate CAR constructs using cell numbers that are orders of magnitude lower than other assays, greatly enhancing our throughput and capabilities.

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