Development of a human monoclonal antibody for potential therapy of CD27-expressing lymphoma and leukemia

Clin Cancer Res. 2012 Jul 15;18(14):3812-21. doi: 10.1158/1078-0432.CCR-11-3308. Epub 2012 May 15.


Purpose: 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.

Experimental design: 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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / genetics
  • Antibodies, Monoclonal* / immunology
  • Antibodies, Monoclonal* / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Cell Proliferation
  • Humans
  • Leukemia* / drug therapy
  • Leukemia* / immunology
  • Lymphoma* / drug therapy
  • Lymphoma* / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Mice, Transgenic
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • T-Lymphocytes* / drug effects
  • T-Lymphocytes* / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7* / genetics
  • Tumor Necrosis Factor Receptor Superfamily, Member 7* / immunology


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • varlilumab