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

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_5C6DC9E7849D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
T-cell activation by treatment of cancer patients with EMD 521873 (Selectikine), an IL-2/anti-DNA fusion protein.
Périodique
Journal of Translational Medicine
Auteur(s)
Laurent J., Touvrey C., Gillessen S., Joffraud M., Vicari M., Bertrand C., Ongarello S., Liedert B., Gallerani E., Beck J., Omlin A., Sessa C., Quaratino S., Stupp R., Gnad-Vogt U.S., Speiser D.E.
ISSN
1479-5876 (Electronic)
ISSN-L
1479-5876
Statut éditorial
Publié
Date de publication
2013
Volume
11
Numéro
5
Pages
1-12
Langue
anglais
Notes
Publication types: Journal Article Publication Status: epublish. PDF type: Research
Résumé
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.
Pubmed
Web of science
Open Access
Oui
Création de la notice
21/02/2013 18:46
Dernière modification de la notice
20/08/2019 15:14
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