1. SIRPα-specific monoclonal antibody enables antibody-dependent phagocytosis of neuroblastoma cells
- Author
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Claudia Rossig, Meriem Bahri, Sarah Vermeulen, François Paris, Sareetha Kailayangiri, Stéphane Birklé, Sophie Fougeray, Natacha Galopin, Bernardo, Elizabeth, Endothelium Radiobiology and Targeting (CRCINA-ÉQUIPE 14), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), University Children's Hospital Muenster, Université de Nantes (UN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
- Subjects
Cancer Research ,medicine.drug_class ,Macrophage ,medicine.medical_treatment ,Phagocytosis ,Immunology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,CD47 Antigen ,Monoclonal antibody ,Antibodies ,03 medical and health sciences ,Mice ,Neuroblastoma ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Cell Line, Tumor ,Gangliosides ,medicine ,Immunology and Allergy ,Animals ,Humans ,Innate immune checkpoint ,Receptors, Immunologic ,biology ,Chemistry ,Antibody-dependent phagocytosis ,CD47 ,Macrophages ,Antibody-Dependent Cell Cytotoxicity ,Antibodies, Monoclonal ,Immunotherapy ,medicine.disease ,Flow Cytometry ,Disialoganglioside ,Antigens, Differentiation ,3. Good health ,Up-Regulation ,Cytolysis ,Oncology ,Microscopy, Fluorescence ,biology.protein ,Cancer research ,Antibody ,030215 immunology - Abstract
International audience; 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.
- Published
- 2020