TY - JOUR A1 - Schneider, Rudolf A1 - Korsak, B. A1 - Almeida, G. M. A1 - Rocha, S. A1 - Pereira, C. A1 - Mendes, N. A1 - Osorio, H. A1 - Pereira, P. M. A1 - Rodrigues, J. M. M. A1 - Sarmento, B. A1 - Tome, J. P. C. A1 - Oliveira, C. T1 - Porphyrin modified trastuzumab improves efficacy of HER2 targeted photodynamic therapy of gastric cancer JF - Cancer Therapy and Prevention N2 - 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 similar to 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. KW - Photoimmunotherapy KW - Photoimmunoconjugate KW - Gastric cancer PY - 2017 DO - https://doi.org/10.1002/ijc.30844 SN - 0020-7136 VL - 141 IS - 7 SP - 1478 EP - 1489 PB - International Journal of Cancer AN - OPUS4-43315 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -