Harnessing MerTK agonism for targeted therapeutics.

Kedage, Vivekananda; Ellerman, Diego; Chen, Yongmei; Liang, Wei-Ching; Borneo, Joven; Wu, Yan; Yan, Minhong

Kedage, Vivekananda; Ellerman, Diego; Chen, Yongmei; Liang, Wei-Ching; Borneo, Joven; Wu, Yan; Yan, Minhong.

Afiliação

Kedage V; Department of Molecular Oncology, Genentech, South San Francisco, CA, USA.
Ellerman D; Department of Protein Chemistry, Genentech, South San Francisco, CA, USA.
Chen Y; Department of Antibody Engineering, Genentech, South San Francisco, CA, USA.
Liang WC; Department of Antibody Engineering, Genentech, South San Francisco, CA, USA.
Borneo J; Department of Immunology and Infectious Diseases, Genentech, South San Francisco, CA, USA.
Wu Y; Department of Antibody Engineering, Genentech, South San Francisco, CA, USA.
Yan M; Department of Molecular Oncology, Genentech, South San Francisco, CA, USA.

MAbs ; 12(1): 1685832, 2020.

Article em En | MEDLINE | ID: mdl-31852344

ABSTRACT

ABSTRACT

Phagocytosis plays important roles both in homeostasis and under pathological conditions. FcÎ³ receptor-mediated phagocytosis has been exploited as an integral mechanism for antibody-based therapies. Unlike FcÎ³ receptor-mediated phagocytosis, MerTK-mediated phagocytic clearance is immunologically silent. Here, we describe a bispecific antibody approach to harness MerTK for targeted clearance without inducing proinflammatory cytokine release associated with FcÎ³ receptor engagement. We generated bispecific antibodies targeting live B cells or amyloid beta aggregates to demonstrate the feasibility and versatility of this new approach.

Assuntos

Peptídeos beta-Amiloides/imunologia; Anticorpos Biespecíficos/metabolismo; Linfócitos B/metabolismo; Macrófagos/metabolismo; Microglia/metabolismo; c-Mer Tirosina Quinase/agonistas; Animais; Anticorpos Biespecíficos/genética; Antígenos CD20/imunologia; Antígenos CD20/metabolismo; Linfócitos B/imunologia; Células Cultivadas; Citocinas/metabolismo; Humanos; Tolerância Imunológica; Mediadores da Inflamação/metabolismo; Macrófagos/imunologia; Camundongos; Camundongos Knockout; Terapia de Alvo Molecular; Fagocitose; Receptores de IgG/metabolismo; c-Mer Tirosina Quinase/genética; c-Mer Tirosina Quinase/imunologia

Palavras-chave

FcÎ³ receptor; MerTK; Phagocytosis; bispecific antibody; immunologically silent

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos B / Peptídeos beta-Amiloides / Microglia / Anticorpos Biespecíficos / C-Mer Tirosina Quinase / Macrófagos Limite: Animals / Humans Idioma: En Revista: MAbs Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos

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