IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-020-20488-3.html
   My bibliography  Save this article

CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells

Author

Listed:
  • Mario Bunse

    (Department of Microenvironmental Regulation in Autoimmunity and Cancer)

  • Janina Pfeilschifter

    (Department of Microenvironmental Regulation in Autoimmunity and Cancer)

  • Julia Bluhm

    (Department of Translational Tumorimmunology)

  • Maria Zschummel

    (Department of Microenvironmental Regulation in Autoimmunity and Cancer)

  • Jara J. Joedicke

    (Department of Microenvironmental Regulation in Autoimmunity and Cancer)

  • Anthea Wirges

    (Department of Translational Tumorimmunology)

  • Helen Stark

    (Department of Translational Tumorimmunology)

  • Vivien Kretschmer

    (Department of Microenvironmental Regulation in Autoimmunity and Cancer)

  • Markus Chmielewski

    (University Hospital Cologne)

  • Wolfgang Uckert

    (Department of Molecular Cell Biology and Gene Therapy)

  • Hinrich Abken

    (University Hospital Regensburg)

  • Jörg Westermann

    (Department of Hematology, Oncology and Tumorimmunology)

  • Armin Rehm

    (Department of Translational Tumorimmunology)

  • Uta E. Höpken

    (Department of Microenvironmental Regulation in Autoimmunity and Cancer)

Abstract

CAR-T cell therapy targeting CD19 demonstrated strong activity against advanced B cell leukemia, however shows less efficacy against lymphoma with nodal dissemination. To target both B cell Non-Hodgkin’s lymphoma (B-NHLs) and follicular T helper (Tfh) cells in the tumor microenvironment (TME), we apply here a chimeric antigen receptor (CAR) that recognizes human CXCR5 with high avidity. CXCR5, physiologically expressed on mature B and Tfh cells, is also highly expressed on nodal B-NHLs. Anti-CXCR5 CAR-T cells eradicate B-NHL cells and lymphoma-supportive Tfh cells more potently than CD19 CAR-T cells in vitro, and they efficiently inhibit lymphoma growth in a murine xenograft model. Administration of anti-murine CXCR5 CAR-T cells in syngeneic mice specifically depletes endogenous and malignant B and Tfh cells without unexpected on-target/off-tumor effects. Collectively, anti-CXCR5 CAR-T cells provide a promising treatment strategy for nodal B-NHLs through the simultaneous elimination of lymphoma B cells and Tfh cells of the tumor-supporting TME.

Suggested Citation

  • Mario Bunse & Janina Pfeilschifter & Julia Bluhm & Maria Zschummel & Jara J. Joedicke & Anthea Wirges & Helen Stark & Vivien Kretschmer & Markus Chmielewski & Wolfgang Uckert & Hinrich Abken & Jörg We, 2021. "CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20488-3
    DOI: 10.1038/s41467-020-20488-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-20488-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-20488-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20488-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.