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

Journal of Translational Medicine

Daniel E Speiser⁸  Ulrike S Gnad-Vogt⁷  Roger Stupp²  Sonia Quaratino⁴  Cristiana Sessa⁵  Aurelius Omlin⁶  Joachim Beck³  Elisa Gallerani⁵  Bernd Liedert⁴  Stefano Ongarello⁴  Caroline Bertrand⁹  Manuela Vicari⁹  Magali Joffraud⁹  Silke Gillessen⁶  Cedric Touvrey¹  Julien Laurent⁴ 

[1] IRBA antenne CRSSA, La Tonche, France;Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland;University of Mainz, Mainz, Germany;Global Clinical Development Unit-Oncology, Merck KGaA, Frankfurter Str. 250, D-64293, Darmstadt, Germany;Oncology Institute of Southern Switzerland, Bellinzona, Switzerland;Kantonsspital, St. Gallen, Switzerland;CureVac GmbH, Frankfurt, Germany;Clinical Tumor Biology & Immunotherapy Unit, Ludwig Center of the University of Lausanne, Lausanne, Switzerland;Division of Experimental Oncology, Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

关键词: Cancer-testis antigen;    Lymphocytes;    Tumor;    Fusion protein;    Interleukin-2;   

Others  :  828252
DOI  :  10.1186/1479-5876-11-5

 received in 2012-08-22, accepted in 2012-12-21,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Laurent et al.; licensee BioMed Central Ltd.

【 图 表 】

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