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Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist

Author

Listed:
  • Giulia Parisi

    (David Geffen School of Medicine at UCLA)

  • Justin D. Saco

    (David Geffen School of Medicine at UCLA)

  • Felix B. Salazar

    (David Geffen School of Medicine at UCLA)

  • Jennifer Tsoi

    (David Geffen School of Medicine at UCLA)

  • Paige Krystofinski

    (David Geffen School of Medicine at UCLA)

  • Cristina Puig-Saus

    (David Geffen School of Medicine at UCLA)

  • Ruixue Zhang

    (David Geffen School of Medicine at UCLA)

  • Jing Zhou

    (Isoplexis Corporation)

  • Gardenia C. Cheung-Lau

    (David Geffen School of Medicine at UCLA)

  • Alejandro J. Garcia

    (David Geffen School of Medicine at UCLA)

  • Catherine S. Grasso

    (David Geffen School of Medicine at UCLA
    Parker Institute for Cancer Immunotherapy)

  • Richard Tavaré

    (Regeneron Pharmaceuticals, Inc.)

  • Siwen Hu-Lieskovan

    (David Geffen School of Medicine at UCLA)

  • Sean Mackay

    (Isoplexis Corporation)

  • Jonathan Zalevsky

    (Nektar Therapeutics)

  • Chantale Bernatchez

    (University of Texas MD Anderson Cancer Center)

  • Adi Diab

    (University of Texas MD Anderson Cancer Center)

  • Anna M. Wu

    (David Geffen School of Medicine at UCLA
    Beckman Research Institute of the City of Hope)

  • Begoña Comin-Anduix

    (David Geffen School of Medicine at UCLA
    Parker Institute for Cancer Immunotherapy
    University of California)

  • Deborah Charych

    (Nektar Therapeutics
    Third Rock Ventures)

  • Antoni Ribas

    (David Geffen School of Medicine at UCLA
    David Geffen School of Medicine at UCLA
    Parker Institute for Cancer Immunotherapy
    University of California)

Abstract

Interleukin-2 (IL-2) is a component of most protocols of adoptive cell transfer (ACT) therapy for cancer, but is limited by short exposure and high toxicities. NKTR-214 is a kinetically-engineered IL-2 receptor βγ (IL-2Rβγ)-biased agonist consisting of IL-2 conjugated to multiple releasable polyethylene glycol chains resulting in sustained signaling through IL-2Rβγ. We report that ACT supported by NKTR-214 increases the proliferation, homing and persistence of anti-tumor T cells compared to ACT with IL-2, resulting in superior antitumor activity in a B16-F10 murine melanoma model. The use of NKTR-214 increases the number of polyfunctional T cells in murine spleens and tumors compared to IL-2, and enhances the polyfunctionality of T and NK cells in the peripheral blood of patients receiving NKTR-214 in a phase 1 trial. In conclusion, NKTR-214 may have the potential to improve the antitumor activity of ACT in humans through increased in vivo expansion and polyfunctionality of the adoptively transferred T cells.

Suggested Citation

  • Giulia Parisi & Justin D. Saco & Felix B. Salazar & Jennifer Tsoi & Paige Krystofinski & Cristina Puig-Saus & Ruixue Zhang & Jing Zhou & Gardenia C. Cheung-Lau & Alejandro J. Garcia & Catherine S. Gra, 2020. "Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-12901-3
    DOI: 10.1038/s41467-019-12901-3
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