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

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.

• 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
• Journal: Journal of translational medicine (J Transl Med) Vol. 11 Pg. 5 (Jan 07 2013) ISSN: 1479-5876 [Electronic] England
• PMID: 23294527 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• EMD 521873
• Interleukin-2
• Recombinant Fusion Proteins
• DNA

Topics

• Antineoplastic Agents (therapeutic use)
• Cell Proliferation
• DNA (immunology)
• Flow Cytometry
• Humans
• Immunohistochemistry
• Interleukin-2 (immunology)
• Lymphocyte Activation
• Lymphocyte Count
• Neoplasms (drug therapy)
• Recombinant Fusion Proteins (therapeutic use)
• Survival Analysis
• T-Lymphocytes (cytology)