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

Anna Emde 1 Chaluvally-Raghavan Pradeep 1 Daniela Aleida Ferraro 1 Nir Ben-Chetrit 1 Michael Sela 1 Benjamin Ribba 2 Zvi Kam 1 Yosef Yarden 1 
2 NUMED - Numerical Medicine
UMPA-ENSL - Unité de Mathématiques Pures et Appliquées, Inria Grenoble - Rhône-Alpes
Abstract : 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.
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Submitted on : Thursday, November 22, 2012 - 7:16:34 PM
Last modification on : Tuesday, October 25, 2022 - 4:23:37 PM

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Anna Emde, Chaluvally-Raghavan Pradeep, Daniela Aleida Ferraro, Nir Ben-Chetrit, Michael Sela, et al.. Combining epitope-distinct antibodies to HER2: cooperative inhibitory effects on invasive growth.. Oncogene, 2011, 30 (14), pp.1631-42. ⟨10.1038/onc.2010.547⟩. ⟨hal-00756354⟩



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