Tettamanti S, Rotiroti MC, Arcangeli S, et al. Lenalidomide Enhances CD23.CAR T Cell Therapy in Chronic Lymphocytic Leukemia. Leukemia & Lymphoma. 2022; (doi: 10.1080/10428194.2022.2043299).
The tumor microenvironment (TME) observed in chronic lymphocytic leukemia (CLL) patients exhibits immunosuppressive behavior that affects the efficacy of chimeric antigen receptor (CAR) T-cells, but pairing the cells with lenalidomide may be a solution. Researchers engineered T cells from patients with CLL to express a CAR directed at the antigen CD23, which has demonstrated therapeutic potential in this patient population. While the CLL TME normally keeps CAR T cells from doing their job effectively, adding lenalidomide — an immunomodulatory agent — allowed CD23.CAR+ T cells to execute effector functions related to antigen-specific cytotoxicity, cytokine release, and proliferation. Lenalidomide maintained functional CAR T-CLL cell immune synapses. In a xenograft model of CLL, CD23.CAR+ T cells efficiently migrated to leukemic sites and slowed disease progression when delivered in tandem with lenalidomide versus with rhIL-2. The study authors believe their findings have positive implications for CAR-based treatment of CLL.