Integrated assays of single-cell dynamics and molecular phenotype for cell therapy manufacturing

ABSTRACT
Cell and gene therapies have revolutionized treatment options for patients with pace of discovery and
implementation accelerating. For example, clinical success of CAR-T cells for hematologic malignancies has led
to use in expanded patient populations and trials targeting for other cancer types. While there are many cell
therapies in preclinical development and clinical trials confidence in their successes is undermined by the
inherent complexity of cells that remains difficult to decipher using existing tools. What is needed is an integrated
analytical platform providing a matrix of readouts that reveal an in-depth real-time understanding of cell
phenotype and metabolism. Such a platform will inform on the therapeutic potential before administration and by
sampling patients will reveal aspects of cell behavior that correlate with efficacy. CellChorus is answering this
need using our platform (“TIMING”) to undertake large scale single-cell analyses to track and characterize
behavior of immune cells over time. TIMING uses sophisticated AI-based software, many years in development,
to track and characterize behaviors of thousands of cells in parallel using time-lapse imaging. Multiple papers
and repeat customers have helped validate our approach to commercialization. Based on users’ demand, we
propose to advance TIMING by (i) developing and optimizing reagents and protocols to identify a suite of cell
surface attributes, (ii) quantify proliferative capacity and (iii) determine metabolic activity before, during, and after
cell-cell interactions. We will integrate these findings with our AI software to provide end users with a simple,
unified assay system to run in their own laboratories on commercially available imaging instrumentation. The
results of this project will be ready-to-use kits to reveal critical immune-biology of cells in critical and challenging
environments. This is predicted to augment translational research and development leading to improvements in
manufacturing and success in patients.

Grant Number: 4R44TR005137-02
NIH Institute/Center: NIH
Principal Investigator: Rebecca Berdeaux