Lenalidomide Enhances the Function of CS1 Chimeric Antigen Receptor-Redirected T Cells Against Multiple Myeloma

Clin Cancer Res. 2018 Jan 1;24(1):106-119. doi: 10.1158/1078-0432.CCR-17-0344. Epub 2017 Oct 23.


Purpose: Multiple myeloma remains an incurable malignancy of plasma cells despite considerable advances in treatment. The purpose of the study was to develop novel chimeric antigen receptors (CAR) for the treatment of multiple myeloma and explore combinatorial therapy using CAR T cells and immunomodulatory drugs such as lenalidomide for increasing treatment efficacy.Experimental Design: We redirected central memory T cells to express second-generation CAR-specific for CS1 and adoptively transferred them into multiple myeloma tumor-bearing mice to test their anti-multiple myeloma activity. CS1 CAR T cells were transduced and expanded in the presence of lenalidomide in vitro The phenotype and effector function of CS1 CAR T cells treated with and without lenalidomide were compared. Finally, CS1 CAR T cells and lenalidomide were administered to treat multiple myeloma-bearing mice as combinatorial therapy.Results: CS1 CAR T cells exhibited efficient antitumor activity when adoptively transferred into mice. Mechanistic studies indicated that the addition of lenalidomide during CS1 CAR T-cell expansion in vitro enhanced the immune functions of CS1 CAR T cells, including cytotoxicity, memory maintenance, Th1 cytokine production, and immune synapse formation. Furthermore, lenalidomide enhanced the antitumor activity and persistence of adoptively transferred CS1 CAR T cells in vivoConclusions: The study demonstrates that lenalidomide improves the anti-multiple myeloma properties of CS1-directed CAR T cells and provides a basis for a planned clinical trial using the combination of lenalidomide with engineered T cells against CS1 in relapsed myeloma. Clin Cancer Res; 24(1); 106-19. ©2017 AACR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunologic Factors / pharmacology
  • Immunological Synapses / immunology
  • Immunotherapy, Adoptive
  • Lenalidomide / pharmacology*
  • Mice
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / metabolism*
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / metabolism*
  • Signaling Lymphocytic Activation Molecule Family / genetics*
  • Signaling Lymphocytic Activation Molecule Family / immunology
  • T-Cell Antigen Receptor Specificity / drug effects
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Xenograft Model Antitumor Assays


  • Angiogenesis Inhibitors
  • Immunologic Factors
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen
  • SLAMF7 protein, human
  • Signaling Lymphocytic Activation Molecule Family
  • Lenalidomide