Ibrutinib Improves Function of CAR T-Cell Therapy for CLL

A study published in the International Journal of Cancer found that administering ibrutinib during chimeric antigen receptor (CAR) T-cell culture can enhance function of patient‐derived CAR T-cell products in patients with chronic lymphocytic leukemia (CLL).

CAR T-cell treatment efficacy appears inferior for treating CLL compared with diffuse large B-cell lymphoma or acute lymphocytic leukemia, and impaired T-cell fitness in these patients may be correlated with treatment failure, according to the study authors. Less-differentiated naïve-like T-cells play an important role in CAR-T expansion and long-term persistence in vivo, and these cells are scarce in patients with CLL.

In this study, researchers sought to assess the effect of the Bruton tyrosine kinase inhibitor ibrutinib, which is approved to treat CLL, on CAR T-cell production. They obtained peripheral blood mononuclear cells from nine healthy donors, and eight patients with CLL were used to generate CAR T-cells. Researchers evaluated T-cell expansion and phenotype, expression of homing and exhaustion makers, and functionality of CAR T-cells.

The findings revealed that CAR T-cell generation in the presence of ibrutinib increased cell viability and expansion of CLL patient-derived CAR T-cells. Ibrutinib also enriched CAR T-cells with less-differentiated naïve-like phenotype and decreased expression of exhaustion markers, including PD-1, TIM-3, and LAG-3. Researchers observed that ibrutinib increased the cytokine release capacity of CLL patient-derived CAR T-cells.