IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46310-y.html
   My bibliography  Save this article

Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma

Author

Listed:
  • C. Grandclément

    (Ichnos Glenmark Innovation)

  • C. Estoppey

    (Ichnos Glenmark Innovation)

  • E. Dheilly

    (Ichnos Glenmark Innovation)

  • M. Panagopoulou

    (Ichnos Glenmark Innovation)

  • T. Monney

    (Ichnos Glenmark Innovation)

  • C. Dreyfus

    (Ichnos Glenmark Innovation)

  • J. Loyau

    (Ichnos Glenmark Innovation)

  • V. Labanca

    (Ichnos Glenmark Innovation)

  • A. Drake

    (Ichnos Glenmark Innovation)

  • S. Angelis

    (Ichnos Glenmark Innovation)

  • A. Rubod

    (Ichnos Glenmark Innovation)

  • J. Frei

    (Ichnos Glenmark Innovation)

  • L. N. Caro

    (Ichnos Glenmark Innovation)

  • S. Blein

    (Ichnos Glenmark Innovation)

  • E. Martini

    (Ichnos Glenmark Innovation)

  • M. Chimen

    (Ichnos Glenmark Innovation)

  • T. Matthes

    (University Hospital Geneva)

  • Z. Kaya

    (Botnar Institute, University of Oxford)

  • C. M. Edwards

    (Botnar Institute, University of Oxford)

  • J. R. Edwards

    (Botnar Institute, University of Oxford)

  • E. Menoret

    (Nantes Université, Inserm, CNRS, Université d’Angers)

  • C. Kervoelen

    (Nantes Université, Inserm, CNRS, Université d’Angers)

  • C. Pellat-Deceunynck

    (Nantes Université, Inserm, CNRS, Université d’Angers
    SIRIC ILIAD, Angers)

  • P. Moreau

    (Nantes Université, Inserm, CNRS, Université d’Angers
    SIRIC ILIAD, Angers
    Unité d’Investigation Clinique, CHU)

  • M. L. Mbow

    (Ichnos Glenmark Innovation)

  • A. Srivastava

    (Ichnos Glenmark Innovation)

  • M. R. Dyson

    (Ichnos Glenmark Innovation)

  • E. A. Zhukovsky

    (Ichnos Glenmark Innovation)

  • M. Perro

    (Ichnos Glenmark Innovation)

  • S. Sammicheli

    (Ichnos Glenmark Innovation)

Abstract

Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma.

Suggested Citation

  • C. Grandclément & C. Estoppey & E. Dheilly & M. Panagopoulou & T. Monney & C. Dreyfus & J. Loyau & V. Labanca & A. Drake & S. Angelis & A. Rubod & J. Frei & L. N. Caro & S. Blein & E. Martini & M. Chi, 2024. "Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46310-y
    DOI: 10.1038/s41467-024-46310-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46310-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-46310-y?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:15:y:2024:i:1:d:10.1038_s41467-024-46310-y. 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.