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Lenalidomide enhances CD23.CAR T cell therapy in chronic lymphocytic leukemia.
- Source :
- Leukemia & Lymphoma; Jul2022, Vol. 63 Issue 7, p1566-1579, 14p
- Publication Year :
- 2022
-
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<superscript>+</superscript> 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<superscript>−/−</superscript>γ<subscript>c</subscript><superscript>−/−</superscript>-based xenograft model of CLL, we demonstrated that, when combined with low-dose lenalidomide, CD23.CAR<superscript>+</superscript> T cells efficiently migrated to leukemic sites and delayed disease progression when compared to CD23.CAR<superscript>+</superscript> T cells given with rhIL-2. These observations underline the therapeutic potential of this novel CAR-based combination strategy in CLL. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10428194
- Volume :
- 63
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Leukemia & Lymphoma
- Publication Type :
- Academic Journal
- Accession number :
- 157908595
- Full Text :
- https://doi.org/10.1080/10428194.2022.2043299