Combining epitope-distinct antibodies to HER2: Cooperative inhibitory effects on invasive growth

Anna Maria Emde, C-R Pradeep, D. A. Ferraro, Chetrit, Nir Ben Chetrit, M. Sela, B. Ribba, Zvi Kam, Yosef Yarden

Research output: Contribution to journalArticlepeer-review


Monoclonal antibodies (mAbs) to HER2 are currently used to treat breast cancer, but low clinical efficacy, along with primary and acquired resistance to therapy, commonly limit clinical applications. We previously reported that combinations of antibodies directed at non-overlapping epitopes of HER2 are endowed with enhanced antitumor effects, probably due to accelerated receptor degradation. Here, we extend these observations to three-dimensional mammary cell models, and compare the effects of single mAbs with the effects of antibody combinations. Collectively, our in vitro assays and computational image analyses indicate that combining mAbs against different epitopes of HER2 better inhibits invasive growth. Importantly, while growth factors are able to reduce intraluminal apoptosis and induce an invasive phenotype, combinations of mAbs better than single mAbs can reverse the growth factor-induced phenotypes of HER2-overexpressing spheroids. In conclusion, our studies propose that mAb combinations negate the biological effects of growth factors on invasive growth of HER2-overexpressing cells. Hence, combining mAbs offers a therapeutic strategy, potentially able to enhance clinical efficacy of existing antireceptor immunotherapeutics.

Original languageEnglish
Pages (from-to)1631-1642
Number of pages12
Issue number14
StatePublished - 7 Apr 2011

All Science Journal Classification (ASJC) codes

  • Genetics
  • Molecular Biology
  • Cancer Research


Dive into the research topics of 'Combining epitope-distinct antibodies to HER2: Cooperative inhibitory effects on invasive growth'. Together they form a unique fingerprint.

Cite this