TY - JOUR
T1 - Lenalidomide enhances CD23.CAR T cell therapy in chronic lymphocytic leukemia
AU - Tettamanti, Sarah
AU - Rotiroti, Maria Caterina
AU - Giordano Attianese, Greta Maria Paola
AU - Arcangeli, Silvia
AU - Zhang, Ronghua
AU - Banerjee, Priyanka
AU - Galletti, Giovanni
AU - McManus, Sheighlah
AU - Mazza, Massimiliano
AU - Nicolini, Fabio
AU - Martinelli, Giovanni
AU - Ivan, Cristina
AU - Veliz Rodriguez, Tania
AU - Barbaglio, Federica
AU - Scarfò, Lydia
AU - Ponzoni, Maurilio
AU - Wierda, William
AU - Gandhi, Varsha
AU - Keating, Michael
AU - Biondi, Andrea
AU - Caligaris-Cappio, Federico
AU - Biagi, Ettore
AU - Ghia, Paolo
AU - Bertilaccio, Maria Teresa Sabrina
N1 - Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - CAR T cells
KW - CD23
KW - Chronic lymphocytic leukemia
KW - immunomodulation
KW - immunotherapy
KW - lenalidomide
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U2 - 10.1080/10428194.2022.2043299
DO - 10.1080/10428194.2022.2043299
M3 - Article
C2 - 35259043
AN - SCOPUS:85126377133
SN - 1042-8194
VL - 63
SP - 1566
EP - 1579
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 7
ER -