CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-09-26

AUTHORS

J Chu, Y Deng, D M Benson, S He, T Hughes, J Zhang, Y Peng, H Mao, L Yi, K Ghoshal, X He, S M Devine, X Zhang, M A Caligiuri, C C Hofmeister, J Yu

ABSTRACT

Multiple myeloma (MM) is an incurable hematological malignancy. Chimeric antigen receptor (CAR)-expressing T cells have been demonstrated successfully in the clinic to treat B-lymphoid malignancies. However, the potential utility of antigen-specific CAR-engineered natural-killer (NK) cells to treat MM has not been explored. In this study, we determined whether CS1, a surface protein that is highly expressed on MM cells, can be targeted by CAR NK cells to treat MM. We successfully generated a viral construct of a CS1-specific CAR and expressed it in human NK cells. In vitro, CS1-CAR NK cells displayed enhanced MM cytolysis and interferon-γ (IFN-γ) production, and showed a specific CS1-dependent recognition of MM cells. Ex vivo, CS1-CAR NK cells also showed similarly enhanced activities when responding to primary MM tumor cells. More importantly, in an aggressive orthotopic MM xenograft mouse model, adoptive transfer of NK-92 cells expressing CS1-CAR efficiently suppressed the growth of human IM9 MM cells and also significantly prolonged mouse survival. Thus, CS1 represents a viable target for CAR-expressing immune cells, and autologous or allogeneic transplantation of CS1-specific CAR NK cells may be a promising strategy to treat MM. More... »

PAGES

917-927

Journal

TITLE

Leukemia

ISSUE

4

VOLUME

28

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/leu.2013.279

    DOI

    http://dx.doi.org/10.1038/leu.2013.279

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1050860950

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/24067492


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    350 schema:name Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA
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    353 grid-institutes:grid.413944.f schema:alternateName Blood and Marrow Transplantation Program, The James Cancer Hospital, The Ohio State University, Columbus, OH, USA
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    355 Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA
    356 The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
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