Your browser doesn't support javascript.
loading
An agonistic anti-signal regulatory protein α antibody for chronic inflammatory diseases.
Xie, Markus M; Dai, Bingbing; Hackney, Jason A; Sun, Tianhe; Zhang, Juan; Jackman, Janet K; Jeet, Surinder; Irizarry-Caro, Ricardo A; Fu, Yongyao; Liang, Yuxin; Bender, Hannah; Shamir, Eliah R; Keir, Mary E; Bevers, Jack; Nakamura, Gerald; Townsend, Michael J; Fox, David A; Scherl, Alexis; Lee, Wyne P; Martin, Flavius; Godowski, Paul J; Pappu, Rajita; Yi, Tangsheng.
Afiliación
  • Xie MM; Department of Immunology Discovery, Genentech, Inc., South San Francisco, CA, USA.
  • Dai B; Department of Immunology Discovery, Genentech, Inc., South San Francisco, CA, USA.
  • Hackney JA; Department of OMNI Biomarker Development, Genentech, Inc., South San Francisco, CA, USA.
  • Sun T; Department of Immunology Discovery, Genentech, Inc., South San Francisco, CA, USA.
  • Zhang J; Department of Translational Immunology, Genentech, Inc., South San Francisco, CA, USA.
  • Jackman JK; Department of Immunology Discovery, Genentech, Inc., South San Francisco, CA, USA.
  • Jeet S; Department of Translational Immunology, Genentech, Inc., South San Francisco, CA, USA.
  • Irizarry-Caro RA; Department of Immunology Discovery, Genentech, Inc., South San Francisco, CA, USA; Department of Human Pathobiology and OMNI Reverse Translation, Genentech, Inc., South San Francisco, CA, USA.
  • Fu Y; Department of Discovery Oncology, Genentech, Inc., South San Francisco, CA, USA.
  • Liang Y; Department of Microchemistry, Proteomics, and Lipidomics and Next Generation Sequencing, Genentech, Inc., South San Francisco, CA, USA.
  • Bender H; Department of Pathology, Genentech, Inc., South San Francisco, CA, USA.
  • Shamir ER; Department of Pathology, Genentech, Inc., South San Francisco, CA, USA.
  • Keir ME; Department of Human Pathobiology and OMNI Reverse Translation, Genentech, Inc., South San Francisco, CA, USA.
  • Bevers J; Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA.
  • Nakamura G; Department of Antibody Engineering, Genentech, Inc., South San Francisco, CA, USA.
  • Townsend MJ; Department of Human Pathobiology and OMNI Reverse Translation, Genentech, Inc., South San Francisco, CA, USA.
  • Fox DA; Division of Rheumatology, Clinical Autoimmunity Center of Excellence, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Scherl A; Department of Pathology, Genentech, Inc., South San Francisco, CA, USA.
  • Lee WP; Department of Translational Immunology, Genentech, Inc., South San Francisco, CA, USA.
  • Martin F; Department of Immunology Discovery, Genentech, Inc., South San Francisco, CA, USA.
  • Godowski PJ; Department of Immunology Discovery, Genentech, Inc., South San Francisco, CA, USA. Electronic address: godowski89@gmail.com.
  • Pappu R; Department of Immunology Discovery, Genentech, Inc., South San Francisco, CA, USA. Electronic address: Pappu.Rajita@gene.com.
  • Yi T; Department of Immunology Discovery, Genentech, Inc., South San Francisco, CA, USA. Electronic address: tangshengy@gmail.com.
Cell Rep Med ; 4(8): 101130, 2023 08 15.
Article en En | MEDLINE | ID: mdl-37490914
ABSTRACT
Signal regulatory protein (SIRPα) is an immune inhibitory receptor expressed by myeloid cells to inhibit immune cell phagocytosis, migration, and activation. Despite the progress of SIRPα and CD47 antagonist antibodies to promote anti-cancer immunity, it is not yet known whether SIRPα receptor agonism could restrain excessive autoimmune tissue inflammation. Here, we report that neutrophil- and monocyte-associated genes including SIRPA are increased in inflamed tissue biopsies from patients with rheumatoid arthritis and inflammatory bowel diseases, and elevated SIRPA is associated with treatment-refractory ulcerative colitis. We next identify an agonistic anti-SIRPα antibody that exhibits potent anti-inflammatory effects in reducing neutrophil and monocyte chemotaxis and tissue infiltration. In preclinical models of arthritis and colitis, anti-SIRPα agonistic antibody ameliorates autoimmune joint inflammation and inflammatory colitis by reducing neutrophils and monocytes in tissues. Our work provides a proof of concept for SIRPα receptor agonism for suppressing excessive innate immune activation and chronic inflammatory disease treatment.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Colitis / Neoplasias Límite: Humans Idioma: En Revista: Cell Rep Med Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Colitis / Neoplasias Límite: Humans Idioma: En Revista: Cell Rep Med Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos