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

Miriam Y Kim, Washington University School of Medicine in St. Louis
Reyka Jayasinghe, Washington University School of Medicine in St. Louis
Jessica M Devenport, Washington University School of Medicine in St. Louis
Julie K Ritchey, Washington University School of Medicine in St. Louis
Michael P Rettig, Washington University School of Medicine in St. Louis
Julie O'Neal, Washington University School of Medicine in St. Louis
Karl W Staser, Washington University School of Medicine in St. Louis
Krista M Kennerly, Washington University School of Medicine in St. Louis
Alun J Carter, Washington University School of Medicine in St. Louis
Feng Gao, Washington University School of Medicine in St. Louis
Byung Ha Lee, NeoImmuneTech, Inc.
Matthew L Cooper, Washington University School of Medicine in St. Louis
John F DiPersio, Washington University School of Medicine 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.