Long-Acting Recombinant Human Interleukin-7, NT-I7, Increases Cytotoxic CD8 T Cells and Enhances Survival in Mouse Glioma Models

Clin Cancer Res. 2022 Mar 15;28(6):1229-1239. doi: 10.1158/1078-0432.CCR-21-0947.


Purpose: Patients with glioblastoma (GBM) are treated with radiotherapy (RT) and temozolomide (TMZ). These treatments may cause prolonged systemic lymphopenia, which itself is associated with poor outcomes. NT-I7 is a long-acting IL7 that expands CD4 and CD8 T-cell numbers in humans and mice. We tested whether NT-I7 prevents systemic lymphopenia and improves survival in mouse models of GBM.

Experimental design: C57BL/6 mice bearing intracranial tumors (GL261 or CT2A) were treated with RT (1.8 Gy/day × 5 days), TMZ (33 mg/kg/day × 5 days), and/or NT-I7 (10 mg/kg on the final day of RT). We followed the mice for survival while serially analyzing levels of circulating T lymphocytes. We assessed regulatory T cells (Treg) and cytotoxic T lymphocytes in the tumor microenvironment, cervical lymph nodes, spleen, and thymus, and hematopoietic stem and progenitor cells in the bone marrow.

Results: GBM tumor-bearing mice treated with RT+NT-I7 increased T lymphocytes in the lymph nodes, thymus, and spleen, enhanced IFNγ production, and decreased Tregs in the tumor which was associated with a significant increase in survival. NT-I7 also enhanced central memory and effector memory CD8 T cells in lymphoid organs and tumor. Depleting CD8 T cells abrogated the effects of NT-I7. Furthermore, NT-I7 treatment decreased progenitor cells in the bone marrow.

Conclusions: In orthotopic glioma-bearing mice, NT-I7 mitigates RT-related lymphopenia, increases cytotoxic CD8 T lymphocytes systemically and in the tumor, and improves survival. A phase I/II trial to evaluate NT-I7 in patients with high-grade gliomas is ongoing (NCT03687957).

Publication types

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

MeSH terms

  • Animals
  • Brain Neoplasms* / pathology
  • CD8-Positive T-Lymphocytes
  • Cell Line, Tumor
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Disease Models, Animal
  • Glioblastoma*
  • Glioma* / pathology
  • Humans
  • Immunologic Factors / pharmacology
  • Interleukin-7
  • Lymphopenia*
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Fusion Proteins
  • T-Lymphocytes, Cytotoxic / pathology
  • Temozolomide / pharmacology
  • Tumor Microenvironment


  • Immunologic Factors
  • Interleukin-7
  • Recombinant Fusion Proteins
  • efineptakin alfa
  • Temozolomide

Associated data

  • ClinicalTrials.gov/NCT03687957