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

Nat Commun. 2022 Jun 13;13(1):3296. doi: 10.1038/s41467-022-30860-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Proliferation
  • Humans
  • Interleukin-7 / pharmacology
  • Mice
  • Neoplasms*
  • Receptors, Chimeric Antigen*
  • Recombinant Fusion Proteins
  • T-Lymphocytes

Substances

  • Interleukin-7
  • Receptors, Chimeric Antigen
  • Recombinant Fusion Proteins
  • efineptakin alfa