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Phase I study of the anti insulin-like growth factor 1 receptor (IGF-1R) monoclonal antibody, AVE1642, as single agent and in combination with bortezomib in patients with relapsed multiple myeloma

Leukemia volume 25, pages 872–874 (2011)Cite this article

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The insulin-like growth factor (IGF) signaling system is comprised of the IGF ligands (IGF-1 and IGF-2), the cell surface receptors that mediate the biological effects of the IGFs (IGF-1 receptor (IGF-1R), IGF-2 receptor and the insulin receptor), as well as a family of circulating IGF-binding proteins. Insulin-like growth factors 1 and 2 have a critical physiological role in the growth and development of many tissues, and are also implicated in various pathological conditions, particularly in multiple myeloma (MM). Primary cells from patients or MM cell lines are particularly sensitive to IGF-1 and IGF-1R inhibition.1, 2 IGF-1R (CD221) is aberrantly expressed on MM cells in about 75% of the cases and is associated with disease severity.1, 2, 3 It was also shown that IGF-1R (CD221) signaling attenuates responsiveness of MM cells to proapoptotic agents, including dexamethasone, cytotoxics, or proteasome inhibitors.2 IGF-1R is therefore an attractive therapeutic target for MM treatment based on the hypothesis that inhibition of IGF-1R function would result in growth inhibition and apoptosis of tumor cells, particularly in combination with other chemotherapeutic drugs and especially proteasome inhibitors.4

AVE1642 is a humanized version of the murine monoclonal antibody, EM164, raised against the human IGF-1R.5 It has been shown to bind specifically, with a high affinity, to human and monkey IGF-1R, to inhibit IGF-1 binding and receptor activation, and to downregulate the receptor by internalization and degradation. AVE1642 has been able to delay growth and survival of some cancer cells in vitro, human tumor xenografts in nude mice, and to inhibit proliferation and survival of most MM cells (primary cells from patients or MM cell lines).4

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Authors and Affiliations

  1. Hematology Department, University Hospital, Nantes, France

    P Moreau

  2. Hematology Department, University Hospital, Torino, Italy

    F Cavallo & M Boccadoro

  3. Hematology Department, University Hospital, Lille, France

    X Leleu & T Facon

  4. Hematology Department, University Hospital, Nancy, France

    C Hulin

  5. Inserm UMR892, Nantes, France

    M Amiot & G Descamps

  6. Sanofi-Aventis, Alfortville, France

    D Mignard

  7. Cancer Center Gauducheau, Saint-Herblain, France

    J L Harousseau

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  1. P Moreau
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Correspondence to J L Harousseau.

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Moreau, P., Cavallo, F., Leleu, X. et al. Phase I study of the anti insulin-like growth factor 1 receptor (IGF-1R) monoclonal antibody, AVE1642, as single agent and in combination with bortezomib in patients with relapsed multiple myeloma. Leukemia 25, 872–874 (2011). https://doi.org/10.1038/leu.2011.4

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