SIRPα-specific monoclonal antibody enables antibody-dependent phagocytosis of neuroblastoma cells - Archive ouverte HAL Access content directly
Journal Articles Cancer Immunology, Immunotherapy Year : 2021

SIRPα-specific monoclonal antibody enables antibody-dependent phagocytosis of neuroblastoma cells

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Abstract

Immunotherapy with anti-GD2 monoclonal antibodies (mAbs) provides some benefits for patients with neuroblastoma (NB). However, the therapeutic efficacy remains limited, and treatment is associated with significant neuropathic pain. Targeting O-acetylated GD2 (OAcGD2) by 8B6 mAb has been proposed to avoid pain by more selective tumor cell targeting. Thorough understanding of its mode of action is necessary to optimize this treatment strategy. Here, we found that 8B6-mediated antibody-dependent cellular phagocytosis (ADCP) performed by macrophages is a key effector mechanism. But efficacy is limited by upregulation of CD47 expression on neuroblastoma cells in response to OAcGD2 mAb targeting, inhibiting 8B6-mediated ADCP. Antibody specific for the CD47 receptor SIRPα on macrophages restored 8B6-induced ADCP of CD47-expressing NB cells and improved the antitumor activity of 8B6 mAb therapy. These results identify ADCP as a critical mechanism for tumor cytolysis by anti-disialoganglioside mAb and support a combination with SIRPα blocking agents for effective neuroblastoma therapy.
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Dates and versions

inserm-03240786 , version 1 (28-05-2021)

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Meriem Bahri, Sareetha Kailayangiri, Sarah Vermeulen, Natacha Galopin, Claudia Rossig, et al.. SIRPα-specific monoclonal antibody enables antibody-dependent phagocytosis of neuroblastoma cells. Cancer Immunology, Immunotherapy, 2021, Online ahead of print. ⟨10.1007/s00262-021-02968-7⟩. ⟨inserm-03240786⟩
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