A PTK7-targeted antibody-drug conjugate reduces tumor-initiating cells and induces sustained tumor regressions

Sci Transl Med. 2017 Jan 11;9(372):eaag2611. doi: 10.1126/scitranslmed.aag2611.


Disease relapse after treatment is common in triple-negative breast cancer (TNBC), ovarian cancer (OVCA), and non-small cell lung cancer (NSCLC). Therapies that target tumor-initiating cells (TICs) should improve patient survival by eliminating the cells that can drive tumor recurrence and metastasis. We demonstrate that protein tyrosine kinase 7 (PTK7), a highly conserved but catalytically inactive receptor tyrosine kinase in the Wnt signaling pathway, is enriched on TICs in low-passage TNBC, OVCA, and NSCLC patient-derived xenografts (PDXs). To deliver a potent anticancer drug to PTK7-expressing TICs, we generated a targeted antibody-drug conjugate (ADC) composed of a humanized anti-PTK7 monoclonal antibody, a cleavable valine-citrulline-based linker, and Aur0101, an auristatin microtubule inhibitor. The PTK7-targeted ADC induced sustained tumor regressions and outperformed standard-of-care chemotherapy. Moreover, the ADC specifically reduced the frequency of TICs, as determined by serial transplantation experiments. In addition to reducing the TIC frequency, the PTK7-targeted ADC may have additional antitumor mechanisms of action, including the inhibition of angiogenesis and the stimulation of immune cells. Together, these preclinical data demonstrate the potential for the PTK7-targeted ADC to improve the long-term survival of cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminobenzoates / therapeutic use
  • Animals
  • Antibodies / therapeutic use*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Cell Adhesion Molecules / chemistry*
  • Cell Adhesion Molecules / immunology
  • Cell Line, Tumor
  • Clinical Trials as Topic
  • Female
  • Humans
  • Immunoconjugates / therapeutic use*
  • Immunotherapy / methods
  • Lung Neoplasms / immunology
  • Lung Neoplasms / therapy
  • Macaca fascicularis
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Microtubules / chemistry
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplastic Stem Cells / drug effects*
  • Oligopeptides / therapeutic use
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / therapy
  • Receptor Protein-Tyrosine Kinases / chemistry*
  • Receptor Protein-Tyrosine Kinases / immunology
  • Triple Negative Breast Neoplasms / immunology
  • Triple Negative Breast Neoplasms / therapy
  • Xenograft Model Antitumor Assays


  • Aminobenzoates
  • Antibodies
  • Antineoplastic Agents
  • Cell Adhesion Molecules
  • Immunoconjugates
  • Oligopeptides
  • auristatin
  • PTK7 protein, human
  • Receptor Protein-Tyrosine Kinases