Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 141, Issue 7, Pages 1478-1489Publisher
WILEY
DOI: 10.1002/ijc.30844
Keywords
photoimmunotherapy; photoimmunoconjugate; gastric cancer; HER2; trastuzumab
Categories
Funding
- European Commission Seventh Framework Programme/Marie Curie Initial Training Network (ITN) [316975/2012]
- European Regional Development Fund (ERDF)/COMPETE2020/Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020
- Fundacao para a Ciencia e a Tecnologia (FCT) [POCI-01-0145-FEDER-007274, PEst-C/SAU/LA0003/2013, FCTUID/QUI/00062/2013, FCTUID/QUI/0100/2013]
- ERDF
- PORTUGAL2020
- NORTE2020 [NORTE-01-0145-FEDER-000029]
- FCT [PD/BI/113971/2015, SFRH/BD/113031/2015, SFRH/BD/85941/2012]
- POPH - QREN Type 4.2, European Social Fund (ESF)
- Portuguese Ministry of Science and Technology (MCTES) [IF/00615/2013]
- SO2S ITN PhD fellowship
- Fundação para a Ciência e a Tecnologia [PD/BI/113971/2015, SFRH/BD/113031/2015] Funding Source: FCT
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available