James Lim, PhD, on the Challenges Posed by the Solid Tumor Microenvironment

“[A] lot of these preclinical research methods don't really integrate or include aspects of the tumor microenvironment, and so, when you're performing a cell killing assay, a lot of these assays are performed under nonphysiological conditions—typically being performed under ambient oxygen settings—and you throw in your CAR T-cells, look at cell killing, and you basically generate a figure hopefully showing that you see robust killing and robust cell therapy function. We know that in the solid tumor microenvironment, the screening setting that we're using for preclinical modeling is truly not representative of an in vivo solid tumor microenvironment.”

Many companies and organizations are attempting to replicate the success seen with chimeric antigen receptor T-cell (CAR-T) therapies for hematological malignancies in solid tumor indications. Although, a major challenge in this research, especially in the screening/preclinical stage, is that the efficacy of candidates in in vitro testing does not always translate to in vivo applications. A major reason for this is that the conditions of the solid tumor microenvironment often differ greatly from the conditions used in in vitro tests.

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 assay method for CAR-T therapies that incorporates aspects of the solid tumor microenvironment.

In an interview with CGTLive™, Lim discussed the unique challenges posed by the solid tumor microenvironment when it comes to cell therapy treatments. In particular, he noted that the hypoxia and high-pressure conditions in the solid tumor microenvironment can greatly hinder the ability of CAR T-cells to kill the tumor cells. Lim also discussed the modeling approaches currently used in preclinical research for CAR-T therapies intended to treat solid tumors and the limitations of these methods for predicting whether a candidate will be effective in the treatment of patients.

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.