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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2013

Open Access 01-12-2013 | Research

T-cell activation by treatment of cancer patients with EMD 521873 (Selectikine), an IL-2/anti-DNA fusion protein

Authors: Julien Laurent, Cedric Touvrey, Silke Gillessen, Magali Joffraud, Manuela Vicari, Caroline Bertrand, Stefano Ongarello, Bernd Liedert, Elisa Gallerani, Joachim Beck, Aurelius Omlin, Cristiana Sessa, Sonia Quaratino, Roger Stupp, Ulrike S Gnad-Vogt, Daniel E Speiser

Published in: Journal of Translational Medicine | Issue 1/2013

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Abstract

Background

EMD 521873 (Selectikine or NHS-IL2LT) is a fusion protein consisting of modified human IL-2 which binds specifically to the high-affinity IL-2 receptor, and an antibody specific for both single- and double-stranded DNA, designed to facilitate the enrichment of IL-2 in tumor tissue.

Methods

An extensive analysis of pharmacodynamic (PD) markers associated with target modulation was assessed during a first-in-human phase I dose-escalation trial of Selectikine.

Results

Thirty-nine patients with metastatic or locally advanced tumors refractory to standard treatments were treated with increasing doses of Selectikine, and nine further patients received additional cyclophosphamide. PD analysis, assessed during the first two treatment cycles, revealed strong activation of both CD4+ and CD8+ T-cells and only weak NK cell activation. No dose response was observed. As expected, Treg cells responded actively to Selectikine but remained at lower frequency than effector CD4+ T-cells. Interestingly, patient survival correlated positively with both high lymphocyte counts and low levels of activated CD8+ T-cells at baseline, the latter of which was associated with enhanced T-cell responses to the treatment.

Conclusions

The results confirm the selectivity of Selectikine with predominant T-cell and low NK cell activation, supporting follow-up studies assessing the clinical efficacy of Selectikine for cancer patients.
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Metadata
Title
T-cell activation by treatment of cancer patients with EMD 521873 (Selectikine), an IL-2/anti-DNA fusion protein
Authors
Julien Laurent
Cedric Touvrey
Silke Gillessen
Magali Joffraud
Manuela Vicari
Caroline Bertrand
Stefano Ongarello
Bernd Liedert
Elisa Gallerani
Joachim Beck
Aurelius Omlin
Cristiana Sessa
Sonia Quaratino
Roger Stupp
Ulrike S Gnad-Vogt
Daniel E Speiser
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2013
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-11-5

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Keynote webinar | Spotlight on medication adherence

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Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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