AGS67E, an Anti-CD37 Monomethyl Auristatin E Antibody-Drug Conjugate as a Potential Therapeutic for B/T-Cell Malignancies and AML: A New Role for CD37 in AML

Mol Cancer Ther. 2015 Jul;14(7):1650-60. doi: 10.1158/1535-7163.MCT-15-0067. Epub 2015 May 1.


CD37 is a tetraspanin expressed on malignant B cells. Recently, CD37 has gained interest as a therapeutic target. We developed AGS67E, an antibody-drug conjugate that targets CD37 for the potential treatment of B/T-cell malignancies. It is a fully human monoclonal IgG2 antibody (AGS67C) conjugated, via a protease-cleavable linker, to the microtubule-disrupting agent monomethyl auristatin E (MMAE). AGS67E induces potent cytotoxicity, apoptosis, and cell-cycle alterations in many non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) cell lines and patient-derived samples in vitro. It also shows potent antitumor activity in NHL and CLL xenografts, including Rituxan-refractory models. During profiling studies to confirm the reported expression of CD37 in normal tissues and B-cell malignancies, we made the novel discovery that the CD37 protein was expressed in T-cell lymphomas and in AML. AGS67E bound to >80% of NHL and T-cell lymphomas, 100% of CLL and 100% of AML patient-derived samples, including CD34(+)CD38(-) leukemic stem cells. It also induced cytotoxicity, apoptosis, and cell-cycle alterations in AML cell lines and antitumor efficacy in orthotopic AML xenografts. Taken together, this study shows not only that AGS67E may serve as a potential therapeutic for B/T-cell malignancies, but it also demonstrates, for the first time, that CD37 is well expressed and a potential drug target in AML.

MeSH terms

  • Acute Disease
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Antibody-Dependent Cell Cytotoxicity / drug effects
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Immunoconjugates / immunology
  • Immunoconjugates / pharmacology*
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / immunology
  • Leukemia, Myeloid / metabolism
  • Lymphoma, B-Cell / drug therapy
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / immunology
  • Lymphoma, Non-Hodgkin / metabolism
  • Lymphoma, T-Cell / drug therapy
  • Lymphoma, T-Cell / immunology
  • Lymphoma, T-Cell / metabolism
  • Mice, Inbred NOD
  • Mice, SCID
  • Oligopeptides / immunology
  • Oligopeptides / metabolism
  • Tetraspanins / immunology*
  • Tetraspanins / metabolism
  • Treatment Outcome
  • Tumor Burden / drug effects
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays*


  • AGS67E
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm
  • CD37 protein, human
  • Immunoconjugates
  • Oligopeptides
  • Tetraspanins
  • monomethyl auristatin E