Codelivery of antigen and an immune cell adhesion inhibitor is necessary for efficacy of soluble antigen arrays in experimental autoimmune encephalomyelitis

Joshua O. Sestak, Bradley P. Sullivan, Sharadvi Thati, Laura Northrup, Brittany Hartwell, Lorena Antunez, M. Laird Forrest, Charlotte M. Vines, Teruna J. Siahaan, Cory Berkland

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number14008
Pages (from-to)14008
Number of pages1
JournalMolecular Therapy - Methods and Clinical Development
Volume1
DOIs
StatePublished - Jan 8 2014
Externally publishedYes

Bibliographical note

Funding Information:
We gratefully acknowledge support from the NIAID (R56AI091996). This work was also supported by grants from the National Center for Research Resources (5P20RR016475) and the National Institute of General Medical Sciences (8P20GM103418) from the National Institutes of Health, The Madison and Lila Self Graduate Fellowship (University of Kansas), and The Institute for Advancing Medical Innovation Graduate Fellowship (University of Kansas).

Publisher Copyright:
© 2014 The American Society of Gene & Cell Therapy.

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