James Lim, PhD, on the Impact of Manufacturing Conditions on CAR-T Efficacy

“We've been able to generate insights using our potency screening assay where cell therapy products grown under nonphysiological conditions show the hallmark features of exhaustion once they're screened under low oxygen and in high pressure environments—they essentially don't kill the tumor cells. Now you can take the same cells and perform a cell killing assay under ambient conditions and you'll see robust killing, which is as expected, because they were generated and produced that way.”

Although numerous studies have attempted to replicate the success seen in treating hematological malignancies with chimeric antigen receptor T-cell (CAR-T) therapies in solid tumor indications, many of these studies have not been successful. Part of the reason for this lack of success is that CAR T-cells manufactured under nonphysiological conditions tend to be ineffective at killing cancer cells in the conditions of 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”, that 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 discussed various approaches that are being used in investigational cell therapy products to attempt to overcome the solid tumor microenvironment and emphasized that the manufacturing process may be another area of interest for addressing this challenge. He noted that Xcell Biosciences is currently developing technologies intended to model the solid tumor microenvironment during manufacturing of CAR T-cells by reducing oxygen levels and increasing pressure. Lim pointed out that the results of the study presented at AACR, which found that cell therapy product manufactured under such conditions showed heightened cytolytic activity under screening conditions that model the solid tumor microenvironment, support the potential of this approach.

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.