Can Ibrutinib Enhance CAR T-Cell Production for Patients With CLL?
Posted: Wednesday, January 6, 2021
For patients with chronic lymphocytic leukemia (CLL), Bruton’s tyrosine kinase (BTK) inhibition and interleukin‐2–inducible T‐cell kinase (ITK) inhibition with ibrutinib during chimeric antigen receptor (CAR) T-cell generation may improve patient-derived CAR T-cell products and potentially enhance CAR T-cell function, according to findings presented in the International Journal of Cancer. Leopold Sellner, MD, of the Heidelberg University Hospital, Germany, and colleagues concluded that ibrutinib-supplemented CAR T-cell production might increase CAR T-cell yields and enrichment of less-differentiated T cells with lower expression of exhauster markers.
“Optimization of the CAR T-cell production process may be a simple but effective approach to improve efficacy of CAR T cells in CLL patients,” the authors noted.
For this analysis of the effects of ibrutinib-supplemented CAR T-cell production, the authors analyzed peripheral blood mononuclear cells from nine healthy donors and CAR T cells from eight patients with CLL. They then evaluated T-cell expansion and phenotype, expression of homing and exhaustion makers, and functionality of CAR T cells.
The authors found that CAR T-cell generation in the presence of ibrutinib resulted in increased cell viability and expansion of CAR T cells from patients with CLL. Additionally, ibrutinib enhanced CAR T cells with a less-differentiated naive-like phenotype and decreased expression of exhaustion makers (including PD-1, TIM-3, and LAG-3). Ibrutinib also increased the cytokine-release capacity of CAR T cells from patients with CLL.
“PD‐1 is a key immune‐checkpoint receptor expressed on activated T cells.… LAG‐3 and TIM‐3 can also negatively impact T‐cell function and induce cell death,” the authors added. “Reduced expression of these negative regulators of T cells may increase immune activation and decrease CAR T-cell exhaustion.”
Disclosure: For full disclosure of the study authors, visit wiley.com.
