Related Experiment Video

Updated: Feb 10, 2026

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
11:34

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers

Published on: December 5, 2017

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Using antibody directed phototherapy to target oesophageal adenocarcinoma with heterogeneous HER2 expression

Hayley Pye1, Mohammed Adil Butt1,2, Laura Funnell1

  • 1Department for Tissue and Energy, Division of Surgery and Interventional Science, University College London, London, UK.

Oncotarget
|May 26, 2018
PubMed

Insights

A new antibody-photosensitizer drug effectively targets and destroys residual esophageal adenocarcinoma cells after resection. This targeted phototherapy shows promise for treating both HER2-positive and HER2-negative esophageal cancers.

Area of Science:

  • Oncology
  • Biotechnology
  • Photodynamic Therapy

Background:

  • Early esophageal adenocarcinoma (OA) and dysplasia are treated with endoscopic resection and photodynamic therapy (PDT).
  • Current treatments may miss discrete disease areas, leading to recurrence, and PDT can cause off-target photosensitivity.
  • A need exists for a tumor-specific, light-activated therapeutic agent with optimized pharmacokinetics to eliminate residual cancer cells.

Purpose of the Study:

  • To develop and evaluate a novel small molecule antibody-photosensitizer conjugate targeting human epidermal growth factor receptor 2 (HER2).
  • To assess the efficacy of this conjugate as a targeted phototherapy for esophageal adenocarcinoma in a preclinical mouse model.

Main Methods:

  • Developed a small molecule antibody-photosensitizer conjugate targeting HER2.
  • Tested the conjugate *in vitro* for selective binding to tumor versus normal tissue and for light-dependent cytotoxicity.
  • Evaluated the agent's pharmacokinetic properties and therapeutic effect in an *in vivo* mouse xenograft model of human OA with low/heterogeneous HER2 expression.

Main Results:

  • The conjugate demonstrated selective binding to tumor cells *in vitro*.
  • Light-activated phototherapy with the agent showed cytotoxicity *in vitro*.
  • The phototherapy agent exhibited favorable pharmacokinetics in the *in vivo* OA mouse model, leading to tumor growth arrest in all treated xenografts, irrespective of HER2 expression levels.

Conclusions:

  • The novel antibody-photosensitizer conjugate is a promising therapeutic agent for esophageal adenocarcinoma.
  • This targeted phototherapy demonstrates potential for treating both HER2-positive and HER2-low/negative OA, addressing limitations of current treatments.
Keywords:
HER2antibody drug conjugateheterogeneityoesophageal adenocarcinomaphotodynamic therapy

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