Kim et al. showed that rhIL-7-hyFc, a long-acting, genetically modified human IL-7 (a pro-lymphoid growth factor) fused to an IgD/G4Fc, expanded functional human CD19-CAR T cells in vitro. rhIL-7-hyFc treatment decreased exhaustion and boosted the proliferation, persistence, and specific antitumor activity of human CD19-CAR or CD33-CAR T cells in immune-deficient NSG mice bearing human CD19+ lymphoma or CD33+ leukemia xenografts, and of murine CD19-CAR T cells targeting syngeneic CD19+ tumors in pre-conditioned immune-competent congenic mice, which showed persistent B cell aplasia and immune memory upon tumor rechallenge.
Contributed by Paula Hochman
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.
Author Info: (1) Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. (2) Division of Oncology, Department of Medicine, Washington University in
Author Info: (1) Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. (2) Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. (3) Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. (4) Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. (5) Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. (6) Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. (7) Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. Division of Dermatology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. (8) Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. (9) Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. (10) Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA. (11) NeoImmuneTech, Inc., Rockville, MD, USA. (12) Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. (13) Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA. jdipersi@wustl.edu.
