Article Text

Download PDFPDF

396 NT-I7, a long-acting interleukin-7, promotes expansion of CD8 T cells and NK cells and immune activation in patients with newly diagnosed high-grade gliomas after chemoradiation
  1. Alice Zhou1,
  2. Michael Rettig1,
  3. Jennifer Foltz1,
  4. Jingqin Luo1,
  5. Omar Butt1,
  6. Chai Avvaru1,
  7. Ruth Katumba1,
  8. Albert Kim1,
  9. Gavin Dunn1,
  10. Christopher Abraham1,
  11. Se Hwan Yang2,
  12. Jean Fan2,
  13. Byung Ha Lee2,
  14. NgocDiep Le2,
  15. George Ansstas1,
  16. Tanner Johanns1,
  17. Jiayi Huang1,
  18. Milan Chheda1,
  19. Todd Fehniger1 and
  20. Jian Campian1
  1. 1Washington University in Saint Louis, St. Louis, MO, USA
  2. 2NeoImmuneTech, Inc., Rockville, MD, USA


Background Lymphopenia is common after chemoradiation for treatment of high-grade gliomas (HGG) and is associated with reduced survival.1 Interleukin-7 (IL-7) promotes T-cell maturation and proliferation and is inappropriately low in lymphopenic patients with HGG.2 We previously demonstrated that first-in-class long-acting IL-7, NT-I7 (efineptakin alfa), reverses lymphopenia and improves survival in murine glioma models.3 This study reports the correlative immune changes after NT-I7 treatment in patients with newly diagnosed HGG in a Phase I/II clinical trial.

Methods Enrolled patients had newly diagnosed HGG treated with concurrent radiotherapy (RT) and temozolomide (TMZ) plus adjuvant TMZ every 4 weeks. NT-I7 was administered intramuscularly 1 week after completion of RT/TMZ and then every 12 weeks, for up to 4 total doses. Phase I utilized the 3+3 design to identify the maximum tolerated dose (MTD). Phase II is a double-blinded, placebo-controlled study with 10 patients in each arm. Immune profiling of patients from the Phase I study was performed with multiparametric flow cytometry and multiplex cytokine analysis.

Results Phase I was completed with 19 patients. The most common adverse events were grade 1 or 2 injection site reactions (42%). Two patients had dose-limiting toxicities at 960 µg/kg (grade 3 elevated alanine aminotransferase and grade 3 back pain), prompting the selection of MTD as 720 µg/kg. Preliminary analysis of Phase I subjects demonstrated dose-dependent increases in absolute lymphocyte count (ALC; 1.3X-4.1X fold increase from pre-therapy measurements) that peaked at week 4, before adjuvant TMZ. Flow cytometry analysis of peripheral blood showed a significant increase in the frequency of CD8+ T-cells, CD4+ T-cells, and CD56bright natural killer (NK) cells after NT-I7 administration. There was no change in B cell counts. Expression of the IL-7 receptor (CD127) was downregulated on most immune subsets within 1 week after NT-I7 administration and recovered to baseline by week 4. Serum cytokine analysis showed a rapid and significant increase in tumor necrosis factor (TNF), chemokine ligand 9 (CXCL9), and a trend to higher interferon-gamma (IFNγ), 1 week after NT-I7 administration.

Conclusions NT-I7 is well tolerated when administered after RT/TMZ for HGG patients. NT-I7 administration prompted an increase in ALC, especially cytotoxic T-cells and NK cells. We also observed rapid increases in key cytokines and chemokines, suggesting immune activation. These findings provide insight into the mechanism of action for NT-I7. Phase II enrollment and additional immune profiling correlates are ongoing.

Trial Registration NCT03687957


  1. Mendez JS, Govindan A, Leong J, Gao F, Huang J, Campian JL. Association between treatment-related lymphopenia and overall survival in elderly patients with newly diagnosed glioblastoma. J Neurooncol 2016;127:329.

  2. Campian JL, Ye X, Gladstone DE, Ambady P, Nirschl TR, Borrello I, Golightly M, king KE, Holdhoff M, Karp J, Drake CG, Grossman SA. Pre-radiation lymphocyte harvesting and post-radiation reinfusion in patients with newly diagnosed high grade gliomas. J Neuro-Oncology 2015 1242. 2015;124:307–316.

  3. Ghosh S, Yan R, Thotala S, Jash A, Mahadevan A, Hu T, Lee B, Yang SH, Hallahan D, Chheda M, Thotala D, Campian J. 565 a novel long-acting interleukin-7 agonist, NT-I7, increases cytotoxic CD8+ T cells and enhances survival in mouse glioma models. J Immunother Cancer 2020;8(Suppl 3):A599–A599.

Ethics Approval This study was approved by Washington University’s ethics board (the Human Research Protection Office); approval number 201810185. Study participants provided written informed consent.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.