IRX-2, a novel immunotherapeutic, enhances and protects NK-cell functions in cancer patients

B. Schilling, E. S. Halstead, P. Schuler, M. Harasymczuk, J. E. Egan, T. L. Whiteside

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: IRX-2 is a primary biologic which has been used for the therapy of head and neck squamous cell cancer (HNSCC) with promising clinical results. Since NK-cell function is compromised in HNSCC patients, we tested the eVects of IRX-2 on the restoration of human NK-cell functions in vitro. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from 23 HNSCC patients and 10 normal controls (NC). The NK-cell phenotype and functions were compared before and after culture ± IRX-2 or ± 50 IU/ml rhIL-2. Flow cytometry was used to study the NK-cell phenotype, cytotoxic activity and cytokine expression. Results: Impaired NK-cell cytotoxicity in HNSCC patients was related to lower expression of NKG2D, NKp30 and NKp46 receptors (P < 0.05) and not to a decreased frequency of NK cells. Incubation of patients' NK cells with IRX-2 up-regulated the percentage of receptor-positive NK cells (P < 0.05). It also up-regulated cytotoxicity of patients' NK cells (P < 0.01) more eVectively than rhIL-2 (P < 0.01). IRX-2, but not rhIL-2, protected NK cells from suppression mediated by TGF-β, and it restored (P < 0.05) expression of activating NK-cell receptors and NK-cell cytotoxicity suppressed by TGF-β. Expression of pSMAD was decreased in NK cells treated with IRX-2 but not in those treated with rhIL-2. Conclusions: IRX-2 was more eVective than IL-2 in enhancing NK-cell cytotoxicity and protecting NK-cell function of HNSCC patients in vitro, emphasizing the potential advantage of IRX-2 as a component of future therapies for HNSCC.

Original languageEnglish (US)
Pages (from-to)1395-1405
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume61
Issue number9
DOIs
StatePublished - Sep 2012

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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