Porphyrin modified trastuzumab improves efficacy of HER2 targeted photodynamic therapy of gastric cancer
Year: 2017
Type: article
Abstract: 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.
Source: International Journal of Cancer
DOI: 10.1002/ijc.30844
Institutions: Universidade do Porto, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, University of Aveiro, Federal Institute For Materials Research and Testing, Cooperativa de Ensino Superior Politécnico e Universitário, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Inovapotek Pharmaceutical Research and Development (Portugal), University of Lisbon, Ghent University, Instituto Superior Técnico, Centro de Química Estrutural
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1149819118, G1168686462, G1297482482, G1314954773, G1452531853, G1516346500, G1679186985, G1763632427, G198576669, G2375406851, G254011574, G265847165, G2690645628, G274581676, G3207356259, G323769159, G3516317140, G373603290, G3840324753, G3891694003, G393177772, Unveiling the crosstalk between E-cadherin and CD44-splice variants as a novel strategy to improve drug sensitivity in gastric cancer, Projecto Estratégico - LA 3 - 2013-2014, G4316116677, G4507117049, G450822820, G4712055029, G4724859719, G491858407, G496129201, G498092695, G5163100631, G5224927334, G536623562, G5485649731, G550652063, G5570850665, G5677667711, G5702163051, UID/BIM/04293 .: Instituto de Investigação e Inovação em Saúde, G6193589897, G6280477952, G63770550, G6434508844, G7286975963, G73600392, G7584003722, G773468960, "The Singlet Oxygen Strategy: sustainable oxidation procedures for applications in material science, synthesis, wastewater treatment, diagnostics and therapeutics", G7965899483, DESIGN OF NOVEL GALACTO-DENDRITIC-PHOTOSENSITIZERS: SELECTIVELY TARGETING AND KILLING CANCER CELLS, BD - Deconstructing gastric cancer colonization: The interplay between immune cells, gastric cancer cells and extracellular vesicles, G8487435997, G8997308637, G96847669
OpenAlex ID: W2715435703