title: Development of a human monoclonal antibody for potential therapy of CD27-expressing lymphoma and leukemia.
abstract: OBJECTIVE
  The TNF receptor superfamily member CD27 is best known for its important role in T-cell immunity but is also recognized as a cell-surface marker on a number of B- and T-cell malignancies. In this article, we describe a novel human monoclonal antibody (mAb) specific for CD27 with properties that suggest a potential utility against malignancies that express CD27.
  
  
  METHODS
  The fully human mAb 1F5 was generated using human Ig transgenic mice and characterized by analytical and functional assays in vitro. Severe combined immunodeficient (SCID) mice inoculated with human CD27-expressing lymphoma cells were administered 1F5 to investigate direct antitumor effects. A pilot study of 1F5 was conducted in non-human primates to assess toxicity.
  
  
  RESULTS
  1F5 binds with high affinity and specificity to human and macaque CD27 and competes with ligand binding. 1F5 activates T cells only in combination with T-cell receptor stimulation and does not induce proliferation of primary CD27-expressing tumor cells. 1F5 significantly enhanced the survival of SCID mice bearing Raji or Daudi tumors, which may be mediated through direct effector mechanisms such as antibody-dependent cellular cytotoxicity. Importantly, administration of up to 10 mg/kg of 1F5 to cynomolgus monkeys was well tolerated without evidence of significant toxicity or depletion of circulating lymphocytes.
  
  
  CONCLUSIONS
  Collectively, the data suggest that the human mAb 1F5, which has recently entered clinical development under the name CDX-1127, may provide direct antitumor activity against CD27-expressing lymphoma or leukemia, independent of its potential to enhance immunity through its agonistic properties.
authors.affiliation: Celldex Therapeutics, Inc., Phillipsburg, NJ, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Vitale
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: He
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Thomas
authors.forename: Jennifer
authors.initials: J
authors.lastname: Widger
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weidlick
authors.forename: Andrea
authors.initials: A
authors.lastname: Crocker
authors.forename: Thomas
authors.initials: T
authors.lastname: O'Neill
authors.forename: James
authors.initials: J
authors.lastname: Storey
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Glennie
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Grote
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.forename: Henry
authors.initials: H
authors.lastname: Marsh
authors.forename: Tibor
authors.initials: T
authors.lastname: Keler
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D049109:Cell Proliferation; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000276:immunology; D008223:Lymphoma / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C000622120:varlilumab