Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting

Journal article


Rotolo, A., Caputo Galarce, V., Holubova, M., Baxan, N., Dubois, O., Chaudhry, M.S., Xiao, X., Goudevenou, K., Pitcher, D.S., Petevi, K., Kachramanoglou, C., Iles, S., Naresh, K., Maher, J. and Karadimitris, A. (2018). Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting. Cancer Cell. 34 (4), pp. 596-610. https://doi.org/10.1016/j.ccell.2018.08.017
AuthorsRotolo, A., Caputo Galarce, V., Holubova, M., Baxan, N., Dubois, O., Chaudhry, M.S., Xiao, X., Goudevenou, K., Pitcher, D.S., Petevi, K., Kachramanoglou, C., Iles, S., Naresh, K., Maher, J. and Karadimitris, A.
Abstract

Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19+ B cell lymphomas are often short lived. We tested whether CAR19-engineering of the CD1d-restricted invariant natural killer T (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to eradicate brain lymphomas underpinned an improved tumor-free and overall survival. CD1D transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells against CD19+ chronic lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers.

KeywordsiNKT ; CAR immunotherapy; B cell malignancies
Year2018
JournalCancer Cell
Journal citation34 (4), pp. 596-610
PublisherCell Press
ISSN1535-6108
Digital Object Identifier (DOI)https://doi.org/10.1016/j.ccell.2018.08.017
Publication dates
Print08 Oct 2018
Publication process dates
Accepted30 Aug 2018
Deposited17 Jun 2021
Publisher's version
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Open
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