IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-11719-3.html
   My bibliography  Save this article

Blood–brain barrier permeable nano immunoconjugates induce local immune responses for glioma therapy

Author

Listed:
  • Anna Galstyan

    (Cedars-Sinai Medical Center)

  • Janet L. Markman

    (Cedars-Sinai Medical Center)

  • Ekaterina S. Shatalova

    (Cedars-Sinai Medical Center)

  • Antonella Chiechi

    (Cedars-Sinai Medical Center)

  • Alan J. Korman

    (Bristol-Myers Squibb)

  • Rameshwar Patil

    (Cedars-Sinai Medical Center)

  • Dmytro Klymyshyn

    (Cedars-Sinai Medical Center)

  • Warren G. Tourtellotte

    (Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center)

  • Liron L. Israel

    (Cedars-Sinai Medical Center)

  • Oliver Braubach

    (Cedars-Sinai Medical Center)

  • Vladimir A. Ljubimov

    (Cedars-Sinai Medical Center)

  • Leila A. Mashouf

    (Harvard Medical School)

  • Arshia Ramesh

    (University of California, Los Angeles (UCLA))

  • Zachary B. Grodzinski

    (Cedars-Sinai Medical Center)

  • Manuel L. Penichet

    (David Geffen School of Medicine at University of California, Los Angeles (UCLA)
    David Geffen School of Medicine at University of California, Los Angeles (UCLA)
    University of California, Los Angeles (UCLA)
    University of California, Los Angeles (UCLA))

  • Keith L. Black

    (Cedars-Sinai Medical Center)

  • Eggehard Holler

    (Cedars-Sinai Medical Center
    Universität Regensburg)

  • Tao Sun

    (Cedars-Sinai Medical Center)

  • Hui Ding

    (Cedars-Sinai Medical Center)

  • Alexander V. Ljubimov

    (Cedars-Sinai Medical Center)

  • Julia Y. Ljubimova

    (Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center)

Abstract

Brain glioma treatment with checkpoint inhibitor antibodies to cytotoxic T-lymphocyte-associated antigen 4 (a-CTLA-4) and programmed cell death-1 (a-PD-1) was largely unsuccessful due to their inability to cross blood–brain barrier (BBB). Here we describe targeted nanoscale immunoconjugates (NICs) on natural biopolymer scaffold, poly(β-L-malic acid), with covalently attached a-CTLA-4 or a-PD-1 for systemic delivery across the BBB and activation of local brain anti-tumor immune response. NIC treatment of mice bearing intracranial GL261 glioblastoma (GBM) results in an increase of CD8+ T cells, NK cells and macrophages with a decrease of regulatory T cells (Tregs) in the brain tumor area. Survival of GBM-bearing mice treated with NIC combination is significantly longer compared to animals treated with single checkpoint inhibitor-bearing NICs or free a-CTLA-4 and a-PD-1. Our study demonstrates trans-BBB delivery of tumor-targeted polymer-conjugated checkpoint inhibitors as an effective GBM treatment via activation of both systemic and local privileged brain tumor immune response.

Suggested Citation

  • Anna Galstyan & Janet L. Markman & Ekaterina S. Shatalova & Antonella Chiechi & Alan J. Korman & Rameshwar Patil & Dmytro Klymyshyn & Warren G. Tourtellotte & Liron L. Israel & Oliver Braubach & Vladi, 2019. "Blood–brain barrier permeable nano immunoconjugates induce local immune responses for glioma therapy," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11719-3
    DOI: 10.1038/s41467-019-11719-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-11719-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-019-11719-3?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:10:y:2019:i:1:d:10.1038_s41467-019-11719-3. 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.