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Human cancer-targeted immunity via transgenic hematopoietic stem cell progeny

Author

Listed:
  • Theodore S. Nowicki

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

  • Nataly Naser Al Deen

    (University of California Los Angeles)

  • Cole W. Peters

    (University of California Los Angeles)

  • Begoña Comin-Anduix

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

  • Egmidio Medina

    (University of California Los Angeles)

  • Cristina Puig-Saus

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

  • Ignacio Baselga Carretero

    (University of California Los Angeles)

  • Paula Kaplan-Lefko

    (University of California Los Angeles)

  • Mignonette H. Macabali

    (University of California Los Angeles)

  • Ivan Perez Garcilazo

    (University of California Los Angeles)

  • Daniel Chen

    (University of California Los Angeles)

  • Jia Pang

    (University of California Los Angeles)

  • Beata Berent-Maoz

    (University of California Los Angeles)

  • Salem Haile

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

  • Jonathan Rodriguez

    (University of California Los Angeles)

  • Moe Kawakami

    (University of California Los Angeles)

  • Conner K. Kidd

    (University of California Los Angeles)

  • Ameya Champhekar

    (University of California Los Angeles)

  • Giuseppe Carlucci

    (University of California Los Angeles)

  • Agustin Vega-Crespo

    (University of California Los Angeles)

  • Bartosz Chmielowski

    (University of California Los Angeles
    University of California Los Angeles)

  • Arun Singh

    (University of California Los Angeles)

  • Noah Federman

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

  • Gary M. Schiller

    (University of California Los Angeles
    University of California Los Angeles)

  • Sarah J. Larson

    (University of California Los Angeles
    University of California Los Angeles)

  • Martin Allen-Auerbach

    (University of California Los Angeles
    University of California Los Angeles)

  • Alexandra M. Klomhaus

    (University of California Los Angeles)

  • Jerome Zack

    (University of California Los Angeles
    University of California Los Angeles)

  • David Baltimore

    (California Institute of Technology)

  • Lili Yang

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

  • Donald B. Kohn

    (University of California Los Angeles
    University of California Los Angeles)

  • Owen N. Witte

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

  • Antoni Ribas

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

Abstract

Adoptive transfer of genetically engineered T cells expressing a tumor-antigen-specific transgenic T cell receptor (TCR) can result in clinical responses in a variety of malignancies. However, these responses are frequently short-lived, and patients typically relapse within several months. This phenomenon is largely due to poor persistence of the transgenic T cells, as well as a progressive loss of their functionality and terminal differentiation in vivo. This underscores the need for cell therapy approaches able to sustain the initial antitumor efficacy and lead to long-term antitumor efficacy. Herein, we report the use of tandem cell therapies involving autologous T cells and hematopoietic stem cells engineered to express the NY-ESO-1 TCR for the treatment of solid tumors in a first-in-human phase I clinical trial (NCT03240861). This therapy is shown to be safe, feasible, and leads to initial tumor regression activity. T cell progeny from the HSC progenitors is shown to provide circulating transgenic NY-ESO-1 TCR-T cells, which display tumor-antigen-specific antitumor functionality, without any evidence of anergy or exhaustion. These results demonstrate the utility of transgenic HSCs to generate a self-renewing source of tumor-specific cellular immunotherapy in human participants. Clinicaltrials.gov: NCT NCT03240861

Suggested Citation

  • Theodore S. Nowicki & Nataly Naser Al Deen & Cole W. Peters & Begoña Comin-Anduix & Egmidio Medina & Cristina Puig-Saus & Ignacio Baselga Carretero & Paula Kaplan-Lefko & Mignonette H. Macabali & Ivan, 2025. "Human cancer-targeted immunity via transgenic hematopoietic stem cell progeny," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60816-z
    DOI: 10.1038/s41467-025-60816-z
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