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

Antonia Rotolo, Valentina S. Caputo, Monika Holubova, Nicoleta Baxan, Olivier Dubois, Mohammed Suhail Chaudhry, Xiaolin Xiao, Katerina Goudevenou, David S. Pitcher, Kyriaki Petevi, Carolina Kachramanoglou, Sandra Iles, Kikkeri Naresh, John Maher, Anastasios Karadimitris

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Abstract

Summary 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.
Original languageEnglish
Pages (from-to)596-610.E11
JournalCANCER CELL
Volume34
Issue number4
Early online date8 Oct 2018
DOIs
Publication statusPublished - 8 Oct 2018

Keywords

  • iNKT
  • CAR immunotherapy
  • B cell malignancies

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