Faculty, Staff and Student Publications
Publication Date
7-1-2022
Journal
Leukemia & Lymphoma
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 preserves CD23.CAR T cells in vitro 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
DOI
10.1080/10428194.2022.2043299
PMID
35259043
PMCID
PMC9828187
PubMedCentral® Posted Date
7-1-2023
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
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Bioinformatics Commons, Biomedical Informatics Commons, Hematology Commons, Immunotherapy Commons, Medical Sciences Commons, Oncology Commons