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Using antibody directed phototherapy to target oesophageal adenocarcinoma with heterogeneous HER2 expression
File(s)
Author(s)
Pye, Hayley
Butt, Mohammed Adil
Funnell, Laura
Reinert, Halla W
Puccio, Ignazio
Type
Journal Article
Abstract
Early oesophageal adenocarcinoma (OA) and pre-neoplastic dysplasia may be treated with endoscopic resection and ablative techniques such as photodynamic therapy (PDT). Though effective, discrete areas of disease may be missed leading to recurrence. PDT further suffers from the side effects of off-target photosensitivity. A tumour specific and light targeted therapeutic agent with optimised pharmacokinetics could be used to destroy residual cancerous cells left behind after resection. A small molecule antibody-photosensitizer conjugate was developed targeting human epidermal growth factor receptor 2 (HER2). This was tested in an in vivo mouse model of human OA using a xenograft flank model with clinically relevant low level HER2 expression and heterogeneity. In vitro we demonstrate selective binding of the conjugate to tumour versus normal tissue. Light dependent cytotoxicity of the phototherapy agent in vitro was observed. In an in vivo OA mouse xenograft model the phototherapy agent had desirable pharmacokinetic properties for tumour uptake and blood clearance time. PDT treatment caused tumour growth arrest in all the tumours despite the tumours having a clinically defined low/negative HER2 expression level. This new phototherapy agent shows therapeutic potential for treatment of both HER2 positive and borderline/negative OA.
Date Issued
2018-07-20
Date Acceptance
2018-03-28
Citation
Oncotarget, 2018, 9 (33), pp.22945-22959
URI
DOI
ISSN
1949-2553
Publisher
Impact Journals
Start Page
22945
End Page
22959
Journal / Book Title
Oncotarget
Volume
9
Issue
33
Copyright Statement
© 2018 Pye et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source
are credited.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29796164
PII: 25159
Subjects
HER2
antibody drug conjugate
heterogeneity
oesophageal adenocarcinoma
photodynamic therapy
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-05-01