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Effects of lenalidomide treatment on CAR-redirected T cells derived from CLL patients

ABSTRACT: Significant response rates have been reported in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphomas (DLBCL), mantle cell lymphomas and follicular lymphomas. In contrast, in CTL019 trials, only 26% of CLL patients had durable antitumor responses with dramatic mechanisms of resistance to anti-CD19.CAR T-cell therapy. Low expression of programmed cell death protein 1 (PD1) has been identified as pre-treatment predictor of response in these trials, though the mechanisms responsible for a limited efficacy in CLL remain poorly understood. Additional studies have demonstrated that CD8+ anti-CAR T cells from patients with CLL exhibit impaired metabolic function compared to CD8+ T cells from healthy donors and that these features are associated with T-cell exhaustion and a reduction in T-cell activation and degranulation. Several T-cell defects have been observed in patients with CLL and are mainly related to impaired immune synapse (IS) formation, and these defects could ultimately impact on the CAR T-cell activation and expansion upon antigen encounter. Thus, the purpose of this study was to explore the possibility of using lenalidomide, an immunomodulatory agent that has induced significant, long-lasting responses in CLL patients, to enhance the therapeutic efficacy of CD23.CAR-redirected T cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE178893 | GEO | 2022/02/28

REPOSITORIES: GEO

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