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Updated: Feb 3, 2026

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
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Published on: December 5, 2017

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Avidity-based binding to HER2 results in selective killing of HER2-overexpressing cells by anti-HER2/CD3

Dionysos Slaga1, Diego Ellerman1, T Noelle Lombana1

  • 1Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Science Translational Medicine
|October 19, 2018
PubMed

Insights

A novel bispecific antibody targets HER2-overexpressing solid tumors by leveraging avidity for high selectivity. This approach aims to reduce on-target, off-tumor effects and enhance T cell therapy safety.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Bispecific antibodies face challenges in solid tumor treatment due to off-tumor effects.
  • Lack of tumor-specific targets leads to T cell autoreactivity in normal tissues.

Purpose of the Study:

  • To develop a HER2/CD3 bispecific antibody for selective targeting of HER2-overexpressing tumor cells.
  • To mitigate on-target, off-tumor adverse effects in solid tumor therapy.

Main Methods:

  • Engineered an anti-HER2/CD3 T cell-dependent bispecific (TDB) antibody.
  • Utilized dual low-affinity anti-HER2 Fab arms for avidity-based tumor cell selectivity.
  • Assessed targeting of HER2-overexpressing cells versus low-HER2 expressing normal tissues.

Main Results:

  • The TDB antibody demonstrates high potency against HER2-overexpressing cells.
  • Selectivity achieved by avidity spares normal tissues with low HER2 expression.
  • Results support clinical development of the anti-HER2/CD3 1Fab-immunoglobulin G TDB.

Conclusions:

  • The developed TDB antibody strategy enhances selectivity for solid tumors.
  • This approach offers a potential solution to mitigate adverse effects in T cell-directed therapies.
  • Broad applications for targeting previously challenging solid tumor antigens are enabled.

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