Soluble Antigen Arrays (SAgAs)
The power of this first-in-class therapeutic modality is in its ability to reintroduce tolerance thereby 'curing' the patient of their autoimmune disease rather than treat its symptoms and rendering the patient immunologically compromised
Unique Potential Of SAgAs SAgAs can present disease specific antigen epitopes and effector molecules along a flexible and soluble backbone to target lymphatic drainage and promote interaction with only disease specific immune cells resulting in a more robust tolerogenic cellular response. This results in a safer therapy that can be used to earlier to intercept disease progression and reverse disease course.
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Preclinical in vivo Success
Multiple studies completed in autoimmune disease models such as EAE, NOD, and NMO mice show SAgAs significantly suppressed disease and prevent relapse. Additional studies showed that treatment with SAgAs also skew the immune response toward tolerance and away from disease progression.
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Modeling of SAgAs
SAgAs have been modeled to determine the theoretical structure and potential interactions of the product molecule with multiple systems.
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REFERENCES
1: Hartwell BL, Martinez-Becerra FJ, Chen J, Shinogle H, Sarnowski M, Moore DS, Berkland C. Antigen-Specific Binding of Multivalent Soluble Antigen Arrays Induces Receptor Clustering and Impedes B Cell Receptor Mediated Signaling. Biomacromolecules. 2016 Mar 14;17(3):710-22. doi: 10.1021/acs.biomac.5b01097. Epub 2016 Feb 5. PubMed PMID: 26771518.
2: Hartwell BL, Smalter Hall A, Swafford D, Sullivan BP, Garza A, Sestak JO, Northrup L, Berkland C. Molecular Dynamics of Multivalent Soluble Antigen Arrays Support a Two-Signal Co-delivery Mechanism in the Treatment of Experimental Autoimmune Encephalomyelitis. Mol Pharm. 2016 Jan 19. [Epub ahead of print] PubMed PMID: 26636828.
3: Hartwell BL, Antunez L, Sullivan BP, Thati S, Sestak JO, Berkland C. Multivalent nanomaterials: learning from vaccines and progressing to antigen-specific immunotherapies. J Pharm Sci. 2015 Feb;104(2):346-61. doi:10.1002/jps.24273. Epub 2014 Dec 1. Review. PubMed PMID: 25447598.
4: Thati S, Kuehl C, Hartwell B, Sestak J, Siahaan T, Forrest ML, Berkland C. Routes of administration and dose optimization of soluble antigen arrays in mice with experimental autoimmune encephalomyelitis. J Pharm Sci. 2015 Feb;104(2):714-21. doi: 10.1002/jps.24272. Epub 2014 Dec 1. PubMed PMID:25447242; PubMed Central PMCID: PMC4312227.
5: Northrup L, Sestak JO, Sullivan BP, Thati S, Hartwell BL, Siahaan TJ, Vines CM, Berkland C. Co-delivery of autoantigen and b7 pathway modulators suppresses experimental autoimmune encephalomyelitis. AAPS J. 2014 Nov;16(6):1204-13. doi:10.1208/s12248-014-9671-y. Epub 2014 Oct 9. PubMed PMID: 25297853; PubMed Central PMCID: PMC4389758.
6: Sestak JO, Fakhari A, Badawi AH, Siahaan TJ, Berkland C. Structure, size, and solubility of antigen arrays determines efficacy in experimental autoimmune encephalomyelitis. AAPS J. 2014 Nov;16(6):1185-93. doi: 10.1208/s12248-014-9654-z. Epub 2014 Sep 6. PubMed PMID: 25193268; PubMed Central PMCID: PMC4389745.
7: Sestak JO, Sullivan BP, Thati S, Northrup L, Hartwell B, Antunez L, Forrest ML, Vines CM, Siahaan TJ, Berkland C. Codelivery of antigen and an immune cell adhesion inhibitor is necessary for efficacy of soluble antigen arrays in experimental autoimmune encephalomyelitis. Mol Ther Methods Clin Dev. 2014 Apr 9;1:14008. doi: 10.1038/mtm.2014.8. eCollection 2014. PubMed PMID: 26015953; PubMed Central PMCID: PMC4420258.
2: Hartwell BL, Smalter Hall A, Swafford D, Sullivan BP, Garza A, Sestak JO, Northrup L, Berkland C. Molecular Dynamics of Multivalent Soluble Antigen Arrays Support a Two-Signal Co-delivery Mechanism in the Treatment of Experimental Autoimmune Encephalomyelitis. Mol Pharm. 2016 Jan 19. [Epub ahead of print] PubMed PMID: 26636828.
3: Hartwell BL, Antunez L, Sullivan BP, Thati S, Sestak JO, Berkland C. Multivalent nanomaterials: learning from vaccines and progressing to antigen-specific immunotherapies. J Pharm Sci. 2015 Feb;104(2):346-61. doi:10.1002/jps.24273. Epub 2014 Dec 1. Review. PubMed PMID: 25447598.
4: Thati S, Kuehl C, Hartwell B, Sestak J, Siahaan T, Forrest ML, Berkland C. Routes of administration and dose optimization of soluble antigen arrays in mice with experimental autoimmune encephalomyelitis. J Pharm Sci. 2015 Feb;104(2):714-21. doi: 10.1002/jps.24272. Epub 2014 Dec 1. PubMed PMID:25447242; PubMed Central PMCID: PMC4312227.
5: Northrup L, Sestak JO, Sullivan BP, Thati S, Hartwell BL, Siahaan TJ, Vines CM, Berkland C. Co-delivery of autoantigen and b7 pathway modulators suppresses experimental autoimmune encephalomyelitis. AAPS J. 2014 Nov;16(6):1204-13. doi:10.1208/s12248-014-9671-y. Epub 2014 Oct 9. PubMed PMID: 25297853; PubMed Central PMCID: PMC4389758.
6: Sestak JO, Fakhari A, Badawi AH, Siahaan TJ, Berkland C. Structure, size, and solubility of antigen arrays determines efficacy in experimental autoimmune encephalomyelitis. AAPS J. 2014 Nov;16(6):1185-93. doi: 10.1208/s12248-014-9654-z. Epub 2014 Sep 6. PubMed PMID: 25193268; PubMed Central PMCID: PMC4389745.
7: Sestak JO, Sullivan BP, Thati S, Northrup L, Hartwell B, Antunez L, Forrest ML, Vines CM, Siahaan TJ, Berkland C. Codelivery of antigen and an immune cell adhesion inhibitor is necessary for efficacy of soluble antigen arrays in experimental autoimmune encephalomyelitis. Mol Ther Methods Clin Dev. 2014 Apr 9;1:14008. doi: 10.1038/mtm.2014.8. eCollection 2014. PubMed PMID: 26015953; PubMed Central PMCID: PMC4420258.