Your browser doesn't support javascript.
loading
Targeting primary acute myeloid leukemia with a new CXCR4 antagonist IgG1 antibody (PF-06747143).
Zhang, Yanyan; Saavedra, Erika; Tang, Ruoping; Gu, Yin; Lappin, Patrick; Trajkovic, Dusko; Liu, Shu-Hui; Smeal, Tod; Fantin, Valeria; De Botton, Stephane; Legrand, Ollivier; Delhommeau, Francois; Pernasetti, Flavia; Louache, Fawzia.
Afiliación
  • Zhang Y; INSERM, UMR 1170, 114 rue Edouard Vaillant, 94805, Villejuif, France.
  • Saavedra E; Université Paris-Saclay, Gustave Roussy, Villejuif, France.
  • Tang R; Gustave Roussy, 94805, Villejuif, France.
  • Gu Y; CNRS, GDR 3697, MicroNIT, Villejuif, France.
  • Lappin P; INSERM, UMR 1170, 114 rue Edouard Vaillant, 94805, Villejuif, France.
  • Trajkovic D; Université Paris-Saclay, Gustave Roussy, Villejuif, France.
  • Liu SH; Gustave Roussy, 94805, Villejuif, France.
  • Smeal T; CNRS, GDR 3697, MicroNIT, Villejuif, France.
  • Fantin V; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 938, CDR Saint-Antoine, F-75012, Paris, France.
  • De Botton S; INSERM, UMR_S 938, CDR Saint-Antoine, F-75012, Paris, France.
  • Legrand O; Sorbonne Universités, UPMC Univ Paris 06, GRC n°7, Groupe de Recherche Clinique sur les Myéloproliférations Aiguës et Chroniques MYPAC, F-75012, Paris, France.
  • Delhommeau F; AP-HP, Hôpital St Antoine, Service d'Hématologie clinique et de thérapie cellulaire, F-75012, Paris, France.
  • Pernasetti F; Oncology Research & Development, Pfizer Worldwide Research & Development, San Diego, CA, USA.
  • Louache F; Drug Safety Research & Development, Pfizer, San Diego, CA, USA.
Sci Rep ; 7(1): 7305, 2017 08 04.
Article en En | MEDLINE | ID: mdl-28779088
The chemokine receptor CXCR4 mediates cell anchorage in the bone marrow (BM) microenvironment and is overexpressed in 25-30% of patients with acute myeloid leukemia (AML). Here we have shown that a new CXCR4 receptor antagonist IgG1 antibody (PF-06747143) binds strongly to AML cell lines and to AML primary cells inhibiting their chemotaxis in response to CXCL12. PF-06747143 also induced cytotoxicity in AML cells via Fc-effector function. To characterize the effects of PF-06747143 on leukemia progression, we used two different patient-derived xenograft (PDX) models: Patient 17CXCR4-low and P15CXCR4-high models, characterized by relatively low and high CXCR4 expression, respectively. Weekly administration of PF-06747143 to leukemic mice significantly reduced leukemia development in both models. Secondary transplantation of BM cells from PF-06747143-treated or IgG1 control-treated animals showed that leukemic progenitors were also targeted by PF-06747143. Administration of a single dose of PF-06747143 to PDX models induced rapid malignant cell mobilization into the peripheral blood (PB). These findings support evaluation of this antibody in AML therapy, with particular appeal to patients resistant to chemotherapy and to unfit patients, unable to tolerate intensive chemotherapy.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Receptores CXCR4 / Antineoplásicos Inmunológicos / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Receptores CXCR4 / Antineoplásicos Inmunológicos / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido