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A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity

Author

Listed:
  • Miriam Y. Kim

    (Washington University in St. Louis)

  • Reyka Jayasinghe

    (Washington University in St. Louis)

  • Jessica M. Devenport

    (Washington University in St. Louis)

  • Julie K. Ritchey

    (Washington University in St. Louis)

  • Michael P. Rettig

    (Washington University in St. Louis)

  • Julie O’Neal

    (Washington University in St. Louis)

  • Karl W. Staser

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Krista M. Kennerly

    (Washington University in St. Louis)

  • Alun J. Carter

    (Washington University in St. Louis)

  • Feng Gao

    (Washington University School of Medicine)

  • Byung Ha Lee

    (NeoImmuneTech, Inc.)

  • Matthew L. Cooper

    (Washington University in St. Louis)

  • John F. DiPersio

    (Washington University in St. Louis)

Abstract

Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies. However, a significant proportion of patients experience suboptimal CAR T cell cytotoxicity and persistence that can permit tumor cell escape and disease relapse. Here we show that a prototype pro-lymphoid growth factor is able to enhance CAR T cell efficacy. We demonstrate that a long-acting form of recombinant human interleukin-7 (IL-7) fused with hybrid Fc (rhIL-7-hyFc) promotes proliferation, persistence and cytotoxicity of human CAR T cells in xenogeneic mouse models, and murine CAR T cells in syngeneic mouse models, resulting in long-term tumor-free survival. Thus, rhIL-7-hyFc represents a tunable clinic-ready adjuvant for improving suboptimal CAR T cell activity.

Suggested Citation

  • Miriam Y. Kim & Reyka Jayasinghe & Jessica M. Devenport & Julie K. Ritchey & Michael P. Rettig & Julie O’Neal & Karl W. Staser & Krista M. Kennerly & Alun J. Carter & Feng Gao & Byung Ha Lee & Matthew, 2022. "A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30860-0
    DOI: 10.1038/s41467-022-30860-0
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    Cited by:

    1. Shuhong Li & Licai Shi & Lijun Zhao & Qiaoru Guo & Jun Li & Ze-lin Liu & Zhi Guo & Yu J. Cao, 2024. "Split-design approach enhances the therapeutic efficacy of ligand-based CAR-T cells against multiple B-cell malignancies," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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