A Peptide-Fc opsonin with pan-amyloid reactivity

James S. Foster, Angela D. Williams, Sallie Macy, Tina Richey, Alan Stuckey, Daniel Craig Wooliver, Richa Koul-Tiwari, Emily Martin, Stephen Kennel, Jonathan Wall

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

There is a continuing need for therapeutic interventions for patients with the protein misfolding disorders that result in systemic amyloidosis. Recently, specific antibodies have been employed to treat AL amyloidosis by opsonizing tissue amyloid deposits thereby inducing cell-mediated dissolution and organ improvement. To develop a pan-amyloid therapeutic agent, we have produced an Fc-fusion product incorporating a peptide, p5, which binds many if not all forms of amyloid. This protein, designated Fcp5, expressed in mammalian cells, forms the desired bivalent dimer structure and retains pan-amyloid reactivity similar to the p5 peptide as measured by immunosorbent assays, immunohistochemistry, surface plasmon resonance, and pulldown assays using radioiodinated Fcp5. Additionally, Fcp5 was capable of opsonizing amyloid fibrils in vitro using a pH-sensitive fluorescence assay of phagocytosis. In mice,125 I-labeled Fcp5 exhibited an extended serum circulation time, relative to the p5 peptide. It specifically bound AA amyloid deposits in diseased mice, as evidenced by biodistribution and microautoradiographic methods, which coincided with an increase in active, Iba-1-positive macrophages in the liver at 48 h postinjection of Fcp5. In healthy mice, no specific tissue accumulation was observed. The data indicate that polybasic, pan-amyloid-targeting peptides, in the context of an Fc fusion, can yield amyloid reactive, opsonizing reagents that may serve as next-generation immunotherapeutics.

Original languageEnglish (US)
Article number1082
JournalFrontiers in immunology
Volume8
Issue numberSEP
DOIs
StatePublished - Sep 4 2017
Externally publishedYes

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Opsonin Proteins
Amyloid
Peptides
Amyloid Plaques
Amyloidosis
Proteostasis Deficiencies
Immunosorbents
Surface Plasmon Resonance
Phagocytosis
Fluorescence
Immunohistochemistry
Macrophages
Antibodies
Liver
Therapeutics
Serum

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Foster, J. S., Williams, A. D., Macy, S., Richey, T., Stuckey, A., Wooliver, D. C., ... Wall, J. (2017). A Peptide-Fc opsonin with pan-amyloid reactivity. Frontiers in immunology, 8(SEP), [1082]. https://doi.org/10.3389/fimmu.2017.01082

A Peptide-Fc opsonin with pan-amyloid reactivity. / Foster, James S.; Williams, Angela D.; Macy, Sallie; Richey, Tina; Stuckey, Alan; Wooliver, Daniel Craig; Koul-Tiwari, Richa; Martin, Emily; Kennel, Stephen; Wall, Jonathan.

In: Frontiers in immunology, Vol. 8, No. SEP, 1082, 04.09.2017.

Research output: Contribution to journalArticle

Foster, JS, Williams, AD, Macy, S, Richey, T, Stuckey, A, Wooliver, DC, Koul-Tiwari, R, Martin, E, Kennel, S & Wall, J 2017, 'A Peptide-Fc opsonin with pan-amyloid reactivity', Frontiers in immunology, vol. 8, no. SEP, 1082. https://doi.org/10.3389/fimmu.2017.01082
Foster JS, Williams AD, Macy S, Richey T, Stuckey A, Wooliver DC et al. A Peptide-Fc opsonin with pan-amyloid reactivity. Frontiers in immunology. 2017 Sep 4;8(SEP). 1082. https://doi.org/10.3389/fimmu.2017.01082
Foster, James S. ; Williams, Angela D. ; Macy, Sallie ; Richey, Tina ; Stuckey, Alan ; Wooliver, Daniel Craig ; Koul-Tiwari, Richa ; Martin, Emily ; Kennel, Stephen ; Wall, Jonathan. / A Peptide-Fc opsonin with pan-amyloid reactivity. In: Frontiers in immunology. 2017 ; Vol. 8, No. SEP.
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