title: Robust expansion of dendritic cells in vivo by hydrodynamic FLT3L-FC gene transfer.
abstract: Due to low numbers of endogenous dendritic cells (DCs) in vivo, exogenous DC-poietin Fms-like tyrosine kinase 3-ligand (FLT3L) is routinely used to generate DC for subsequent studies. We engineered a novel FLT3L-FC DNA construct that, when combined with hydrodynamic gene transfer (HDT), induced robust DC expansion in mice. DC generated in vivo by FLT3L-FC HDT produced cytokines in response to stimulation by an array of TLR agonists and promoted T cell proliferation. The FLT3L-FC protein produced in vivo spontaneously homodimerized to enable effective FLT signaling and the FC-domain enhanced its plasma half-life, providing an improved reagent and method to boost DC numbers.
authors: LakePharma Inc., 530 Harbor Blvd., Belmont, CA 94002, USA.
authors: Hua
authors: H
authors: Tu
authors: Palo Alto Veterans Institute for Research & Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave., Palo Alto, CA 94304, USA.
authors: Thomas M
authors: TM
authors: Burke
authors: Palo Alto Veterans Institute for Research & Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave., Palo Alto, CA 94304, USA.
authors: Cecilia
authors: C
authors: Oderup
authors: LakePharma Inc., 530 Harbor Blvd., Belmont, CA 94002, USA.
authors: Kexin
authors: K
authors: Huang
authors: Palo Alto Veterans Institute for Research & Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave., Palo Alto, CA 94304, USA.
authors: Kathryn
authors: K
authors: Wong
authors: Palo Alto Veterans Institute for Research & Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave., Palo Alto, CA 94304, USA.
authors: Susanna
authors: S
authors: Lewén
authors: Stanford University School of Medicine, Department of Pathology, 300 Pasteur Dr., Lane 235, Stanford, CA 94305, USA.
authors: Melissa
authors: M
authors: LaJevic
authors: Palo Alto Veterans Institute for Research & Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave., Palo Alto, CA 94304, USA. Electronic address: bazabel@alum.mit.edu.
authors: Brian A
authors: BA
authors: Zabel
mesh_terms: D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006207:Half-Life; D057446:Hydrodynamics; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000378:metabolism*; D055503:Protein Multimerization; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction
chemical_list: D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C084881:flt3 ligand protein
keywords: Cytokine; Pharmacodynamics; Pharmacokinetics; Progenitor