title: Codelivery of antigen and an immune cell adhesion inhibitor is necessary for efficacy of soluble antigen arrays in experimental autoimmune encephalomyelitis.
abstract: Autoimmune diseases such as multiple sclerosis (MS) are typified by the misrecognition of self-antigen and the clonal expansion of autoreactive T cells. Antigen-specific immunotherapies (antigen-SITs) have long been explored as a means to desensitize patients to offending self-antigen(s) with the potential to retolerize the immune response. Soluble antigen arrays (SAgAs) are composed of hyaluronic acid (HA) cografted with disease-specific autoantigen (proteolipid protein peptide) and an ICAM-1 inhibitor peptide (LABL). SAgAs were designed as an antigen-SIT that codeliver peptides to suppress experimental autoimmune encephalomyelitis (EAE), a murine model of MS. Codelivery of antigen and cell adhesion inhibitor (LABL) conjugated to HA was essential for SAgA treatment of EAE. Individual SAgA components or mixtures thereof reduced proinflammatory cytokines in cultured splenocytes from EAE mice; however, these treatments showed minimal to no in vivo therapeutic effect in EAE mice. Thus, carriers that codeliver antigen and a secondary "context" signal (e.g., LABL) in vivo may be an important design criteria to consider when designing antigen-SIT for autoimmune therapy.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas, USA.
authors.forename: Joshua O
authors.initials: JO
authors.lastname: Sestak
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas, USA.
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Sullivan
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas, USA.
authors.forename: Sharadvi
authors.initials: S
authors.lastname: Thati
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Northrup
authors.affiliation: Bioengineering Graduate Program, University of Kansas , Lawrence, Kansas, USA.
authors.forename: Brittany
authors.initials: B
authors.lastname: Hartwell
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas, USA.
authors.forename: Lorena
authors.initials: L
authors.lastname: Antunez
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas, USA.
authors.forename: M Laird
authors.initials: ML
authors.lastname: Forrest
authors.affiliation: Department of Biological Sciences, University of Texas at El Paso , El Paso, Texas, USA.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Vines
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas, USA.
authors.forename: Teruna J
authors.initials: TJ
authors.lastname: Siahaan
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas, USA ; Bioengineering Graduate Program, University of Kansas , Lawrence, Kansas, USA ; Department of Chemical and Petroleum Engineering, University of Kansas , Lawrence, Kansas, USA.
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland