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

A. Emde C.-R. Pradeep D. A. Ferraro N. Ben-Chetrit M. Sela B. Ribba 1 Z. Kam Y. Yarden
1 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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Article dans une revue
Oncogene, Nature Publishing Group, 2011, 30 (14), pp.1631-42. 〈10.1038/onc.2010.547〉
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https://hal.inria.fr/hal-00756354
Contributeur : Benjamin Ribba <>
Soumis le : jeudi 22 novembre 2012 - 19:16:34
Dernière modification le : jeudi 11 janvier 2018 - 06:24:06

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A. Emde, C.-R. Pradeep, D. A. Ferraro, N. Ben-Chetrit, M. Sela, et al.. Combining epitope-distinct antibodies to HER2: cooperative inhibitory effects on invasive growth.. Oncogene, Nature Publishing Group, 2011, 30 (14), pp.1631-42. 〈10.1038/onc.2010.547〉. 〈hal-00756354〉

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