Porphyrin modified trastuzumab improves efficacy of HER2 targeted photodynamic therapy of gastric cancer

Barbara Korsak, Gabriela M. Almeida, Sara Rocha, Carla Pereira, Nuno Mendes, Hugo Osório, Patrícia M.R. Pereira, João M.M. Rodrigues, Rudolf J. Schneider, Bruno Sarmento, João P.C. Tomé, Carla Oliveira

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Gastric cancer (GC) is the 3rd deadliest cancer worldwide, due to limited treatment options and late diagnosis. Human epidermal growth factor receptor-2 (HER2) is overexpressed in ∼20% of GC cases and anti-HER2 antibody trastuzumab in combination with conventional chemotherapy, is recognized as standard therapy for HER2-positive metastatic GC. This strategy improves GC patients' survival by 2–3 months, however its optimal results in breast cancer indicate that GC survival may be improved. A new photoimmunoconjugate was developed by conjugating a porphyrin with trastuzumab (Trast:Porph) for targeted photodynamic therapy in HER2-positive GC. Using mass spectrometry analysis, the lysine residues in the trastuzumab structure most prone for porphyrin conjugation were mapped. The in vitro data demonstrates that Trast:Porph specifically binds to HER2-positive cells, accumulates intracellularly, co-localizes with lysosomal marker LAMP1, and induces massive HER2-positive cell death upon cellular irradiation. The high selectivity and cytotoxicity of Trast:Porph based photoimmunotherapy is confirmed in vivo in comparison with trastuzumab alone, using nude mice xenografted with a HER2-positive GC cell line. In the setting of human disease, these data suggest that repetitive cycles of Trast:Porph photoimmunotherapy may be used as an improved treatment strategy in HER2-positive GC patients.

Original languageEnglish
Pages (from-to)1478-1489
Number of pages12
JournalInternational Journal of Cancer
Issue number7
StatePublished - Oct 1 2017


  • HER2
  • gastric cancer
  • photoimmunoconjugate
  • photoimmunotherapy
  • trastuzumab


Dive into the research topics of 'Porphyrin modified trastuzumab improves efficacy of HER2 targeted photodynamic therapy of gastric cancer'. Together they form a unique fingerprint.

Cite this