title: Genetic modification of T cells redirected toward CS1 enhances eradication of myeloma cells.
abstract: OBJECTIVE
  Our goal is to test whether CS1 could be targeted by chimeric antigen receptor (CAR) T cells to treat multiple myeloma (MM).
  
  
  METHODS
  We generated a retroviral construct of a CS1-specific CAR and engineered primary human T cells expressing the CAR. We then tested the capacity of CS1-CAR T cells to eradicate human MM tumor cells in vitro, ex vivo, and in vivo using orthotopic MM xenograft mouse models.
  
  
  RESULTS
  In vitro, compared with mock-transduced T cells, upon recognizing CS1-positive MM cells, CS1-CAR-transduced T cells secreted more IFN-γ as well as interleukin (IL)-2, expressed higher levels of the activation marker CD69, showed higher capacity for degranulation, and displayed enhanced cytotoxicity. Ectopically forced expression of CS1 in MM cells with low CS1 expression enhanced recognition and killing by CAR T cells. Ex vivo, CS1-CAR T cells also showed similarly enhanced activities when responding to primary MM cells. More importantly, in orthotopic MM xenograft mouse models, adoptive transfer of human primary T cells expressing CS1-CAR efficiently suppressed the growth of human MM.1S and IM9 myeloma cells and significantly prolonged mouse survival.
  
  
  CONCLUSIONS
  CS1 is a promising antigen that can be targeted by CAR-expressing T cells for treatment of MM.
authors.affiliation: Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.|The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Chu
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Shun
authors.initials: S
authors.lastname: He
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.|Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Youcai
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Peng
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Hughes
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Yi
authors.affiliation: Dardinger Neuro-oncology Center, Department of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Chang-Hyuk
authors.initials: CH
authors.lastname: Kwon
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Qi-En
authors.initials: QE
authors.lastname: Wang
authors.affiliation: Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.|The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.|Blood and Marrow Transplantation Program, The James Cancer Hospital, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Devine
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.|Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: He
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.|Department of Pathology, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Bai
authors.affiliation: Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.|The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Hofmeister
authors.affiliation: Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.|The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.|Blood and Marrow Transplantation Program, The James Cancer Hospital, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005434:Flow Cytometry; D005818:Genetic Engineering; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology; D000071176:Signaling Lymphocytic Activation Molecule Family; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; C448987:SLAMF7 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family