title: Epidermal growth factor receptor-targeted photosensitizer selectively inhibits EGFR signaling and induces targeted phototoxicity in ovarian cancer cells.
abstract: Targeted photosensitizer delivery to EGFR-expressing cells was achieved in the present study using a high purity, targeted photoimmunoconjugate (PIC). When the PDT agent, benzoporphyrin derivative monoacid ring A (BPD) was coupled to an EGFR-targeting antibody (cetuximab), we observed altered cellular localization and selective phototoxicity of EGFR-positive cells, but no phototoxicity of EGFR-negative cells. Cetuximab in the PIC formulation blocked EGF-induced activation of the EGFR and downstream signaling pathways. Our results suggest that photoimmunotargeting is a useful dual strategy for the selective destruction of cancer cells and also exerts the receptor-blocking biological function of the antibody.
authors.affiliation: Wellman Center for Photomedicine, Department of Dermatology, Bartlett Hall 314, Massachusetts General Hospital, Harvard Medical School,40 Blossom Street, Boston, MA 02114, USA.
authors.forename: Adnan O
authors.initials: AO
authors.lastname: Abu-Yousif
authors.forename: Anne C E
authors.initials: AC
authors.lastname: Moor
authors.forename: Xiang
authors.initials: X
authors.lastname: Zheng
authors.forename: Mark D
authors.initials: MD
authors.lastname: Savellano
authors.forename: Weiping
authors.initials: W
authors.lastname: Yu
authors.forename: Pål K
authors.initials: PK
authors.lastname: Selbo
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D000068818:Cetuximab; D017484:Dermatitis, Phototoxic; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D000077362:Verteporfin
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000068818:Cetuximab