An anti-TNF-α antibody mimetic to treat ocular inflammation

Hanieh Khalili; Richard W Lee; Peng T Khaw; Steve Brocchini; Andrew D Dick; David A Copland

doi:10.1038/srep36905

An anti-TNF-α antibody mimetic to treat ocular inflammation

Hanieh Khalili
, Richard W Lee
, Peng T Khaw
, Steve Brocchini
, Andrew D Dick
, David A Copland

Research output: Contribution to journal › Article (Academic Journal) › peer-review

23 Citations (Scopus)

344 Downloads (Pure)

Abstract

Infliximab is an antibody that neutralizes TNF-α and is used principally by systemic administration to treat many inflammatory disorders. We prepared the antibody mimetic Fab-PEG-Fab (FpFinfliximab) for direct intravitreal injection to assess whether such formulations have biological activity and potential utility for ocular use. FpFinfliximab was designed to address side effects caused by antibody degradation and the presence of the Fc region. Surface plasmon resonance analysis indicated that infliximab and FpFinfliximab maintained binding affinity for both human and murine recombinant TNF-α. No Fc mediated RPE cellular uptake was observed for FpFinfliximab. Both Infliximab and FpFinfliximab suppressed ocular inflammation by reducing the number of CD45+ infiltrate cells in the EAU mice after a single intravitreal injection at the onset of peak disease. These results offer an opportunity to develop and formulate for ocular use, FpF molecules designed for single and potentially multiple targets using bi-specific FpFs.

Original language	English
Article number	36905
Number of pages	10
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep36905
Publication status	Published - 22 Nov 2016

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title = "An anti-TNF-α antibody mimetic to treat ocular inflammation",

abstract = "Infliximab is an antibody that neutralizes TNF-α and is used principally by systemic administration to treat many inflammatory disorders. We prepared the antibody mimetic Fab-PEG-Fab (FpFinfliximab) for direct intravitreal injection to assess whether such formulations have biological activity and potential utility for ocular use. FpFinfliximab was designed to address side effects caused by antibody degradation and the presence of the Fc region. Surface plasmon resonance analysis indicated that infliximab and FpFinfliximab maintained binding affinity for both human and murine recombinant TNF-α. No Fc mediated RPE cellular uptake was observed for FpFinfliximab. Both Infliximab and FpFinfliximab suppressed ocular inflammation by reducing the number of CD45+ infiltrate cells in the EAU mice after a single intravitreal injection at the onset of peak disease. These results offer an opportunity to develop and formulate for ocular use, FpF molecules designed for single and potentially multiple targets using bi-specific FpFs.",

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language = "English",

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T1 - An anti-TNF-α antibody mimetic to treat ocular inflammation

AU - Khalili, Hanieh

AU - Lee, Richard W

AU - Khaw, Peng T

AU - Brocchini, Steve

AU - Dick, Andrew D

AU - Copland, David A

PY - 2016/11/22

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AB - Infliximab is an antibody that neutralizes TNF-α and is used principally by systemic administration to treat many inflammatory disorders. We prepared the antibody mimetic Fab-PEG-Fab (FpFinfliximab) for direct intravitreal injection to assess whether such formulations have biological activity and potential utility for ocular use. FpFinfliximab was designed to address side effects caused by antibody degradation and the presence of the Fc region. Surface plasmon resonance analysis indicated that infliximab and FpFinfliximab maintained binding affinity for both human and murine recombinant TNF-α. No Fc mediated RPE cellular uptake was observed for FpFinfliximab. Both Infliximab and FpFinfliximab suppressed ocular inflammation by reducing the number of CD45+ infiltrate cells in the EAU mice after a single intravitreal injection at the onset of peak disease. These results offer an opportunity to develop and formulate for ocular use, FpF molecules designed for single and potentially multiple targets using bi-specific FpFs.

U2 - 10.1038/srep36905

DO - 10.1038/srep36905

M3 - Article (Academic Journal)

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SN - 2045-2322

VL - 6

JO - Scientific Reports

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ER -

An anti-TNF-α antibody mimetic to treat ocular inflammation

Abstract

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