Faculty, Staff and Student Publications

Publication Date

7-1-2022

Journal

Leukemia & Lymphoma

DOI

10.1080/10428194.2022.2043299

PMID

35259043

PMCID

PMC9828187

PubMedCentral® Posted Date

7-1-2023

PubMedCentral® Full Text Version

Author MSS

Abstract

Chimeric antigen receptors (CAR)-modified T cells are an emerging therapeutic tool for chronic lymphocytic leukemia (CLL). However, in patients with CLL, well-known T-cell defects and the inhibitory properties of the tumor microenvironment (TME) hinder the efficacy of CAR T cells. We explored a novel approach combining CARs with lenalidomide, an immunomodulatory drug that tempers the immunosuppressive activity of the CLL TME. T cells from patients with CLL were engineered to express a CAR specific for CD23, a promising target antigen. Lenalidomide maintained the in vitro effector functions of CD23.CAR+ T cells effector functions in terms of antigen-specific cytotoxicity, cytokine release and proliferation. Overall, lenalidomide preserved functional CAR T-CLL cell immune synapses. In a Rag2-/-γc-/--based xenograft model of CLL, we demonstrated that, when combined with low-dose lenalidomide, CD23.CAR+ T cells efficiently migrated to leukemic sites and delayed disease progression when compared to CD23.CAR+ T cells given with rhIL-2. These observations underline the therapeutic potential of this novel CAR-based combination strategy in CLL.

Keywords

Humans, Immunotherapy, Adoptive, Interleukin Receptor Common gamma Subunit, Lenalidomide, Leukemia, Lymphocytic, Chronic, B-Cell, T-Lymphocytes, Tumor Microenvironment, chronic lymphocytic leukemia, CAR T cells, CD23, lenalidomide, immunomodulation, immunotherapy

Published Open-Access

yes

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