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| Página principal > Artículos > Artículos publicados > Enforced sialyl-Lewis-X (sLeX) display in E-selectin ligands by exofucosylation is dispensable for CD19-CAR T-cell activity and bone marrow homing |
(Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Hospital Clínic i Provincial de Barcelona) (Dr von Hauner Children's Hospital, LMU) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
| Fecha: | 2021 |
| Resumen: | CD19-directed chimeric antigen receptors (CAR) T cells induce impressive rates of complete response in advanced B-cell malignancies, specially in B-cell acute lymphoblastic leukemia (B-ALL). However, CAR T-cell-treated patients eventually progress due to poor CAR T-cell persistence and/or disease relapse. The bone marrow (BM) is the primary location for acute leukemia. The rapid/efficient colonization of the BM by systemically infused CD19-CAR T cells might enhance CAR T-cell activity and persistence, thus, offering clinical benefits. Circulating cells traffic to BM upon binding of tetrasaccharide sialyl-Lewis X (sLeX)-decorated E-selectin ligands (sialofucosylated) to the E-selectin receptor expressed in the vascular endothelium. sLeX-installation in E-selectin ligands is achieved through an ex vivo fucosylation reaction. Here, we sought to characterize the basal and cell-autonomous display of sLeX in CAR T-cells activated using different cytokines, and to assess whether exofucosylation of E-selectin ligands improves CD19-CAR T-cell activity and BM homing. We report that cell-autonomous sialofucosylation (sLeX display) steadily increases in culture- and in vivo -expanded CAR T cells, and that, the cytokines used during T-cell activation influence both the degree of such endogenous sialofucosylation and the CD19-CAR T-cell efficacy and persistence in vivo. However, glycoengineered enforced sialofucosylation of E-selectin ligands was dispensable for CD19-CAR T-cell activity and BM homing in multiple xenograft models regardless the cytokines employed for T-cell expansion, thus, representing a dispensable strategy for CD19-CAR T-cell therapy. Glyco-engineered enforced sialofucosylation of E-selectin ligands was dispensable for CD19-CAR T-cell activity and BM homing in multiple xenograft models, thus representing an unnecessary strategy for CD19-CAR T-cell therapy. |
| Ayudas: | "la Caixa" Foundation LCF/PR/HR19/52160011 European Commission 646903 European Commission 811220 Ministerio de Economía y Competitividad SAF2016-80481R Ministerio de Economía y Competitividad SAF2019-108160R |
| Nota: | Altres ajuts: Asociación Española Contra el Cancer; Fundacion Uno entre Cienmil |
| Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Lengua: | Anglès |
| Documento: | Article ; recerca ; Versió publicada |
| Materia: | BM homing ; CAR T-cells ; E-selectin ligands ; Exofucosylation |
| Publicado en: | Clinical and Translational Medicine, Vol. 11 (february 2021) , ISSN 2001-1326 |
