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01.09.2012 | Original Article

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

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 9/2012

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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 effects 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 effectively 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 effective 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.

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Titel: IRX-2, a novel immunotherapeutic, enhances and protects NK-cell functions in cancer patients
Publikationsdatum: 01.09.2012
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 9/2012
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-1197-x

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

Abstract

Background

Methods

Results

Conclusions

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

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Abstract

Background

Methods

Results

Conclusions

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Neu im Fachgebiet Onkologie

Prostatakarzinom: EU initiiert neues Screeningkonzept

Blasenkarzinom – Biomarker statt Zytologie?

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Adjuvante Brustkrebstherapie: Doppelt hält besser

Update Onkologie