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

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 L. Cooper and John F. DiPersio ()
Additional contact information
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
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

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-30860-0

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