IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-14471-1.html
   My bibliography  Save this article

Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy

Author

Listed:
  • Meenu Sharma

    (University of Texas MD Anderson Cancer Center)

  • Hiep Khong

    (University of Texas MD Anderson Cancer Center)

  • Faisal Fa’ak

    (University of Texas MD Anderson Cancer Center)

  • Salah-Eddine Bentebibel

    (University of Texas MD Anderson Cancer Center)

  • Louise M. E. Janssen

    (University of Texas MD Anderson Cancer Center)

  • Brent C. Chesson

    (University of Texas MD Anderson Cancer Center)

  • Caitlin A. Creasy

    (University of Texas MD Anderson Cancer Center)

  • Marie-Andrée Forget

    (University of Texas MD Anderson Cancer Center)

  • Laura Maria S. Kahn

    (University of Texas MD Anderson Cancer Center)

  • Barbara Pazdrak

    (University of Texas MD Anderson Cancer Center)

  • Binisha Karki

    (University of Texas MD Anderson Cancer Center)

  • Yared Hailemichael

    (University of Texas MD Anderson Cancer Center)

  • Manisha Singh

    (University of Texas MD Anderson Cancer Center)

  • Christina Vianden

    (University of Texas MD Anderson Cancer Center)

  • Srinivas Vennam

    (Nektar Therapeutics)

  • Uddalak Bharadwaj

    (The University of Texas MD Anderson Cancer Center)

  • David J. Tweardy

    (The University of Texas MD Anderson Cancer Center)

  • Cara Haymaker

    (University of Texas MD Anderson Cancer Center)

  • Chantale Bernatchez

    (University of Texas MD Anderson Cancer Center)

  • Shixia Huang

    (Baylor College of Medicine
    Dan L. Duncan Cancer Center)

  • Kimal Rajapakshe

    (Baylor College of Medicine)

  • Cristian Coarfa

    (Baylor College of Medicine)

  • Michael E. Hurwitz

    (Yale Comprehensive Cancer Center)

  • Mario Sznol

    (Yale University Cancer Center, Yale University)

  • Patrick Hwu

    (University of Texas MD Anderson Cancer Center)

  • Ute Hoch

    (Nektar Therapeutics)

  • Murali Addepalli

    (Nektar Therapeutics)

  • Deborah H. Charych

    (Nektar Therapeutics)

  • Jonathan Zalevsky

    (Nektar Therapeutics)

  • Adi Diab

    (University of Texas MD Anderson Cancer Center)

  • Willem W. Overwijk

    (University of Texas MD Anderson Cancer Center
    Nektar Therapeutics
    The University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences
    University of Texas MD Anderson Cancer Center)

Abstract

High dose interleukin-2 (IL-2) is active against metastatic melanoma and renal cell carcinoma, but treatment-associated toxicity and expansion of suppressive regulatory T cells (Tregs) limit its use in patients with cancer. Bempegaldesleukin (NKTR-214) is an engineered IL-2 cytokine prodrug that provides sustained activation of the IL-2 pathway with a bias to the IL-2 receptor CD122 (IL-2Rβ). Here we assess the therapeutic impact and mechanism of action of NKTR-214 in combination with anti-PD-1 and anti-CTLA-4 checkpoint blockade therapy or peptide-based vaccination in mice. NKTR-214 shows superior anti-tumor activity over native IL-2 and systemically expands anti-tumor CD8+ T cells while inducing Treg depletion in tumor tissue but not in the periphery. Similar trends of intratumoral Treg dynamics are observed in a small cohort of patients treated with NKTR-214. Mechanistically, intratumoral Treg depletion is mediated by CD8+ Teff-associated cytokines IFN-γ and TNF-α. These findings demonstrate that NKTR-214 synergizes with T cell-mediated anti-cancer therapies.

Suggested Citation

  • Meenu Sharma & Hiep Khong & Faisal Fa’ak & Salah-Eddine Bentebibel & Louise M. E. Janssen & Brent C. Chesson & Caitlin A. Creasy & Marie-Andrée Forget & Laura Maria S. Kahn & Barbara Pazdrak & Binisha, 2020. "Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14471-1
    DOI: 10.1038/s41467-020-14471-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-14471-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-14471-1?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Kateryna Onyshchenko & Ren Luo & Elena Guffart & Simone Gaedicke & Anca-Ligia Grosu & Elke Firat & Gabriele Niedermann, 2023. "Expansion of circulating stem-like CD8+ T cells by adding CD122-directed IL-2 complexes to radiation and anti-PD1 therapies in mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    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:11:y:2020:i:1:d:10.1038_s41467-020-14471-1. 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.