James Lim, PhD, on Simulating the Solid Tumor Microenvironment in Cell Killing Assays

“[I]n the context of autologous cell therapies, there tends to be huge variations between patient cells that could be related to their age, their treatment history, and just the fidelity and the quality of the cells that were obtained in that given moment. And so, because of the inherent diversity and complexity related to autologous cell therapy manufacturing, we think that we could implement our technology during the actual manufacturing process to identify optimal phases or optimal points during the manufacturing in which the cells would have the greatest degree of potency and fidelity. And so, we're utilizing our technology to help inform manufacturing, inform process development, and [it] could also be utilized to predict how a given patient cell therapy product would perform in vivo.”

Currently, cytokine secretion assays are the gold standard for evaluating chimeric antigen receptor T-cell (CAR-T) therapy potency during the manufacturing process. Although, there are limitations to these assays’ predictive capabilities, especially for CAR-T therapies intended to target solid tumors because they do not take into account the conditions presented by the solid tumor microenvironment.

James Lim, PhD, the cofounder and chief scientific officer of Xcell Biosciences, coauthored a poster entitled, “Functional potency assay predicts CAR-T effectiveness in tumor microenvironment”, which was presented at the American Association for Cancer Research (AACR) Annual Meeting 2023, held April 14-19, 2023, in Orlando, Florida. The poster describes a novel cell killing assay method for CAR-T therapies that incorporates an incubation technology with discrete oxygen and pressure control in order to model aspects of the solid tumor microenvironment, namely hypoxia and high-pressure conditions.

In an interview with CGTLive™, Lim described the new technology and gave an overview of the findings from the research. He pointed out that the new method could be a potentially useful tool to complement existing cytokine secretion assays during CAR-T manufacturing workflows. In particular, Lim noted that such an integration has the potential to improve quality testing and better inform the likelihood of ultimate treatment success.

Click here to read more coverage of the AACR 2023 Annual Meeting.

REFERENCES
1. Xing Y, Liu N, Czeryba N, et al. Functional potency assay predicts CAR-T effectiveness in tumor microenvironment. Presented at: AACR Annual Meeting. April 14-19, 2023; Orlando, FL. Abstract 1782.