Augmenting Trastuzumab Therapy Against Breast Cancer Through Selective Activation of NK Cells

Abstract

Trastuzumab, a monoclonal antibody (mAb) targeting HER-2/neu, kills tumor cells by several mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Strategies that enhance the activity of ADCC effectors, including natural killer (NK) cells, may improve trastuzumab s efficacy. NK cells that encounter trastuzumab-coated, HER2-overexpressing breast cancer cells become activated and express CD137, a costimulatory receptor. CD137 activation, which is dependent on the Fc RIII receptor, occurred both in vitro and in the peripheral blood of women with HER2- expressing breast cancer following trastuzumab treatment. Stimulation of trastuzumab-activated NK cells with an agonistic mAb against CD137 killed breast cancer cells more efficiently in vitro and in multiple HER2+ in vivo models.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2013
Accession Number
ADA595679

Entities

People

  • Holbrook Kohrt

Organizations

  • Stanford University

Tags

DTIC Thesaurus Topics

  • Adaptive Immunity
  • Antibodies
  • Biological Factors
  • Blood
  • Breast Cancer
  • Cell Line
  • Cells
  • Diseases And Disorders
  • Immune System
  • Lymphatic Diseases
  • Lymphocytes
  • Molecules
  • Neoplasms
  • Proteins
  • Resistance
  • Targeting
  • Therapy

Fields of Study

  • Biology
  • Medicine

Readers

  • Immunology
  • Oncology (Cancer Research).