Related Experiment Video

Updated: Jan 25, 2026

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
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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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Intracellular Delivery of an Antibody Targeting Gasdermin-B Reduces HER2 Breast Cancer Aggressiveness

Ángela Molina-Crespo1,2, Ana Cadete3,4, David Sarrio1,2

  • 1Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas "Alberto Sols" (CSIC-UAM), IdiPaz, Madrid, Spain.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|May 9, 2019
PubMed
Abstract

Insights

Targeting Gasdermin B (GSDMB) with nanomedicine offers a new strategy for HER2 breast cancers. This approach reduces tumor growth, metastasis, and therapy resistance by delivering an anti-GSDMB antibody intracellularly.

Area of Science:

  • Oncology
  • Nanomedicine
  • Molecular Biology

Background:

  • Gasdermin B (GSDMB) overexpression is prevalent in HER2 breast cancers, correlating with increased cell migration, therapeutic resistance, and poor prognosis.
  • GSDMB's role in promoting aggressive tumor behavior necessitates novel therapeutic strategies targeting its intracellular functions.

Purpose of the Study:

  • To develop and evaluate a targeted nanomedicine for intracellular delivery of an anti-GSDMB antibody in HER2 breast cancer.
  • To investigate the efficacy of this nanomedicine in reducing GSDMB-driven tumor cell migration, enhancing anti-HER2 therapy response, and inhibiting tumor growth and metastasis.

Main Methods:

  • Development of hyaluronic acid-based nanocapsules for targeted intracellular delivery of an anti-GSDMB antibody.
  • In vitro and in vivo testing using HER2 breast cancer cell models and orthotopic xenografts.
  • Assessment of GSDMB binding to sulfatides and its impact on cell death pathways.

Main Results:

  • The anti-GSDMB antibody delivered via nanocapsules specifically reduced GSDMB-induced cell migration in vitro.
  • Nanoparticle-delivered antibody enhanced sensitivity to trastuzumab and reduced tumor growth by increasing apoptosis in vivo.
  • Therapy significantly diminished lung metastasis in MDA-MB-231-HER2 cells and was linked to increased GSDMB-sulfatide binding.

Conclusions:

  • This study presents the first evidence of an effective antibody-based nanomedicine targeting an intracellular oncoprotein (GSDMB).
  • Intracellular delivery of anti-GSDMB antibody successfully inhibited key protumor functions, including migration, metastasis, and therapy resistance.
  • This nanomedicine represents a promising new targeted therapeutic strategy for aggressive HER2-positive breast cancers with poor outcomes.

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