MEN1309/OBT076, a First-In-Class Antibody-Drug Conjugate Targeting CD205 in Solid Tumors

Mol Cancer Ther. 2019 Sep;18(9):1533-1543. doi: 10.1158/1535-7163.MCT-18-0624. Epub 2019 Jun 21.


CD205 is a type I transmembrane glycoprotein and is a member of the C-type lectin receptor family. Analysis by mass spectrometry revealed that CD205 was robustly expressed and highly prevalent in a variety of solid malignancies from different histotypes. IHC confirmed the increased expression of CD205 in pancreatic, bladder, and triple-negative breast cancer (TNBC) compared with that in the corresponding normal tissues. Using immunofluorescence microscopy, rapid internalization of the CD205 antigen was observed. These results supported the development of MEN1309/OBT076, a fully humanized CD205-targeting mAb conjugated to DM4, a potent maytansinoid derivate, via a cleavable N-succinimidyl-4-(2-pyridyldithio) butanoate linker. MEN1309/OBT076 was characterized in vitro for target binding affinity, mechanism of action, and cytotoxic activity against a panel of cancer cell lines. MEN1309/OBT076 displayed selective and potent cytotoxic effects against tumor cells exhibiting strong and low to moderate CD205 expression. In vivo, MEN1309/OBT076 showed potent antitumor activity resulting in durable responses and complete tumor regressions in many TNBC, pancreatic, and bladder cancer cell line-derived and patient-derived xenograft models, independent of antigen expression levels. Finally, the pharmacokinetics and pharmacodynamic profile of MEN1309/OBT076 was characterized in pancreatic tumor-bearing mice, demonstrating that the serum level of antibody-drug conjugate (ADC) achieved through dosing was consistent with the kinetics of its antitumor activity. Overall, our data demonstrate that MEN1309/OBT076 is a novel and selective ADC with potent activity against CD205-positive tumors. These data supported the clinical development of MEN1309/OBT076, and further evaluation of this ADC is currently ongoing in the first-in-human SHUTTLE clinical trial.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • CHO Cells
  • Cell Line, Tumor
  • Cricetulus
  • Female
  • HEK293 Cells
  • HT29 Cells
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / pharmacology*
  • Lectins, C-Type / antagonists & inhibitors*
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism
  • MCF-7 Cells
  • Maytansine / chemistry
  • Maytansine / pharmacology
  • Mice
  • Mice, Nude
  • Mice, SCID
  • Minor Histocompatibility Antigens / immunology
  • Minor Histocompatibility Antigens / metabolism
  • Molecular Targeted Therapy / methods*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Receptors, Cell Surface / antagonists & inhibitors*
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism
  • Xenograft Model Antitumor Assays / methods*


  • Antibodies, Monoclonal
  • Antigens, CD
  • DEC-205 receptor
  • Immunoconjugates
  • Lectins, C-Type
  • Minor Histocompatibility Antigens
  • Receptors, Cell Surface
  • Maytansine