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The Antitumor Activities of Anti-CD47 Antibodies Require Fc-FcγR interactions.
Osorio, Juan C; Smith, Patrick; Knorr, David A; Ravetch, Jeffrey V.
Afiliação
  • Osorio JC; Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY, 10065, USA.
  • Smith P; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
  • Knorr DA; Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY, 10065, USA.
  • Ravetch JV; Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY, 10065, USA.
bioRxiv ; 2023 Jun 29.
Article em En | MEDLINE | ID: mdl-37455857
While anti-CD47 antibodies hold promise for cancer immunotherapy, early phase clinical trials have shown limited signs of clinical benefit, suggesting that blockade of CD47 alone may not be sufficient for effective tumor control. Here, we investigate the contributions of the Fc domain of anti-CD47 antibodies required for optimal in vivo antitumor activity across multiple species-matched models, providing new insights into the mechanisms underlying the efficacy of this emerging class of therapeutic antibodies. Using a novel mouse model humanized for CD47, SIRPα and FcγRs, we demonstrate that local administration of an Fc-engineered anti-CD47 antibody with enhanced binding to activating FcγRs modulates myeloid and T-cell subsets in the tumor microenvironment, resulting in improved long-term systemic antitumor immunity and minimal on-target off-tumor toxicity. Our results highlight the importance of Fc optimization in the development of effective anti-CD47 therapies and provide a novel approach for enhancing the antitumor activity of this promising immunotherapy.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article