dc.contributor.author | Burley, TA | |
dc.contributor.author | Mączyńska, J | |
dc.contributor.author | Shah, A | |
dc.contributor.author | Szopa, W | |
dc.contributor.author | Harrington, KJ | |
dc.contributor.author | Boult, JKR | |
dc.contributor.author | Mrozek-Wilczkiewicz, A | |
dc.contributor.author | Vinci, M | |
dc.contributor.author | Bamber, JC | |
dc.contributor.author | Kaspera, W | |
dc.contributor.author | Kramer-Marek, G | |
dc.date.accessioned | 2018-01-30T15:45:28Z | |
dc.date.issued | 2018-06-01 | |
dc.identifier.citation | International journal of cancer, 2018, 142 (11), pp. 2363 - 2374 | |
dc.identifier.issn | 0020-7136 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1037 | |
dc.identifier.eissn | 1097-0215 | |
dc.identifier.doi | 10.1002/ijc.31246 | |
dc.description.abstract | Glioblastomas (GBMs) are high-grade brain tumors, differentially driven by alterations (amplification, deletion or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just 12-15 months following standard therapy. A combination of interventions targeting tumor-specific cell surface regulators along with convergent downstream signaling pathways may enhance treatment efficacy. Against this background, we investigated a novel photoimmunotherapy approach combining the cytotoxicity of photodynamic therapy with the specificity of immunotherapy. An EGFR-specific affibody (ZEGFR:03115 ) was conjugated to the phthalocyanine dye, IR700DX, which when excited with near-infrared light produces a cytotoxic response. ZEGFR:03115 -IR700DX EGFR-specific binding was confirmed by flow cytometry and confocal microscopy. The conjugate showed effective targeting of EGFR positive GBM cells in the brain. The therapeutic potential of the conjugate was assessed both in vitro, in GBM cell lines and spheroids by the CellTiter-Glo® assay, and in vivo using subcutaneous U87-MGvIII xenografts. In addition, mice were imaged pre- and post-PIT using the IVIS/Spectrum/CT to monitor treatment response. Binding of the conjugate correlated to the level of EGFR expression in GBM cell lines. The cell proliferation assay revealed a receptor-dependent response between the tested cell lines. Inhibition of EGFRvIII+ve tumor growth was observed following administration of the immunoconjugate and irradiation. Importantly, this response was not seen in control tumors. In conclusion, the ZEGFR:03115 -IR700DX showed specific uptake in vitro and enabled imaging of EGFR expression in the orthotopic brain tumor model. Moreover, the proof-of-concept in vivo PIT study demonstrated therapeutic efficacy of the conjugate in subcutaneous glioma xenografts. | |
dc.format | Print-Electronic | |
dc.format.extent | 2363 - 2374 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | WILEY | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Glioblastoma | |
dc.subject | Disease Models, Animal | |
dc.subject | Immunoconjugates | |
dc.subject | Immunotherapy | |
dc.subject | Phototherapy | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.subject | Cell Death | |
dc.subject | Female | |
dc.subject | Molecular Imaging | |
dc.subject | ErbB Receptors | |
dc.subject | Antineoplastic Agents, Immunological | |
dc.title | Near-infrared photoimmunotherapy targeting EGFR-Shedding new light on glioblastoma treatment. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-12-19 | |
rioxxterms.versionofrecord | 10.1002/ijc.31246 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-06 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | International journal of cancer | |
pubs.issue | 11 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Preclinical Molecular Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Preclinical Molecular Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Ultrasound & Optical Imaging | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Preclinical Molecular Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Preclinical Molecular Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Ultrasound & Optical Imaging | |
pubs.publication-status | Published | |
pubs.volume | 142 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Preclinical Molecular Imaging | |
icr.researchteam | Pre-Clinical MRI | |
icr.researchteam | Targeted Therapy | |
icr.researchteam | Ultrasound & Optical Imaging | |
dc.contributor.icrauthor | Harrington, Kevin | |
dc.contributor.icrauthor | Boult, Jessica | |
dc.contributor.icrauthor | Bamber, Jeffrey | |
dc.contributor.icrauthor | Kramer-Marek, Gabriela | |