title: 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.affiliation: Division of Experimental Oncology, Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. julien.laurent@merckgroup.com
authors.forename: Julien
authors.initials: J
authors.lastname: Laurent
authors.forename: Cedric
authors.initials: C
authors.lastname: Touvrey
authors.forename: Silke
authors.initials: S
authors.lastname: Gillessen
authors.forename: Magali
authors.initials: M
authors.lastname: Joffraud
authors.forename: Manuela
authors.initials: M
authors.lastname: Vicari
authors.forename: Caroline
authors.initials: C
authors.lastname: Bertrand
authors.forename: Stefano
authors.initials: S
authors.lastname: Ongarello
authors.forename: Bernd
authors.initials: B
authors.lastname: Liedert
authors.forename: Elisa
authors.initials: E
authors.lastname: Gallerani
authors.forename: Joachim
authors.initials: J
authors.lastname: Beck
authors.forename: Aurelius
authors.initials: A
authors.lastname: Omlin
authors.forename: Cristiana
authors.initials: C
authors.lastname: Sessa
authors.forename: Sonia
authors.initials: S
authors.lastname: Quaratino
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
authors.forename: Ulrike S
authors.initials: US
authors.lastname: Gnad-Vogt
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D049109:Cell Proliferation; D004247:DNA / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000276:immunology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D009369:Neoplasms / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D000970:Antineoplastic Agents; C578499:EMD 521873; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D004247:DNA