Photochemical activation of MH3-B1/rGel: a HER2-targeted treatment approach for ovarian cancer

Oncotarget. 2015 May 20;6(14):12436-51. doi: 10.18632/oncotarget.3814.


HER2-targeted therapy has been shown to have limited efficacy in ovarian cancer despite frequent overexpression of this receptor. Photochemical internalization (PCI) is a modality for cytosolic drug delivery, currently undergoing clinical evaluation. In the present project we studied the application of PCI in combination with the HER2-targeted recombinant fusion toxin, MH3-B1/rGel, for the treatment of ovarian cancer. The SKOV-3 cell line, resistant to trastuzumab- and MH3-B1/rGel- monotherapy, was shown to respond strongly to PCI of MH3-B1/rGel to a similar extent as observed for the treatment-sensitive SK-BR-3 breast cancer cells. Extensive hydrolytic degradation of MH3-B1/rGel in acidic endocytic vesicles was indicated as the mechanism of MH3-B1/rGel resistance in SKOV-3 cells. This was shown by the positive Pearson's correlation coefficient between Alexa488-labeled MH3-B1/rGel and Lysotracker in SKOV-3 cells in contrast to the negative Pearson's correlation coefficient in SK-BR-3 cells. The application of PCI to induce the release of MH3-B1/rGel was also demonstrated to be effective on SKOV-3 xenografts. Application of PCI with MH3-B1/rGel was further found highly effective in the HER2 expressing HOC-7 and NuTu-19 ovarian cancer cell lines. The presented results warrant future development of PCI in combination with MH3-B1/rGel as a novel therapeutic approach in preclinical models of ovarian cancer.

Keywords: HER2/neu/ErbB2; immunotoxin; ovarian cancer; photochemical internalization; photodynamic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Cell Line, Tumor
  • Drug Delivery Systems / methods*
  • Female
  • Humans
  • Immunotoxins / pharmacology*
  • Mice
  • Molecular Targeted Therapy / methods*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Photosensitizing Agents / pharmacology
  • Receptor, ErbB-2 / metabolism*
  • Recombinant Fusion Proteins / pharmacology
  • Single-Chain Antibodies / pharmacology
  • Xenograft Model Antitumor Assays


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Immunotoxins
  • Photosensitizing Agents
  • Recombinant Fusion Proteins
  • Single-Chain Antibodies
  • Receptor, ErbB-2