EFFICACY OF ANTI- INFLAMMATORY SIgAS AFTER TOPICAL TREATMENT IN INFLAMMATORY BOWEL DISEASE...
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EFFICACY OF ANTI- INFLAMMATORY SIgAS AFTER TOPICAL TREATMENT IN INFLAMMATORY BOWEL DISEASE DISCLOSURE R. Arends 1, , R. Ubink 1 , M. van der Lee 1 , G. de Roo 2 , L. Dickey 3 , G. Rouwendal 4 , G. Ariaans 4 , W. Dokter 1 1 Preclinical Department, 2 Bio DSP, 3 LEX Platform 4 New Molecular Entities, Synthon Biopharmaceuticals BV, Nijmegen, The Netherlands B. Weigmann, M. Neurath Department of Gastroenterology, Pneumology and Endocrinology of the Medizinische Klinik 1, Erlangen, Germany B. Corthésy Centre Hospitalier Universitaire Vaudois, R & D Laboratory of the Division of Immunology and Allergy, Lausanne, Switzerland
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Transcript of EFFICACY OF ANTI- INFLAMMATORY SIgAS AFTER TOPICAL TREATMENT IN INFLAMMATORY BOWEL DISEASE...
EFFICACY OF ANTI-INFLAMMATORY SIgAS AFTER TOPICAL TREATMENT IN INFLAMMATORY BOWEL DISEASE
DISCLOSURER. Arends1,, R. Ubink1, M. van der Lee1, G. de Roo2, L. Dickey3, G. Rouwendal4, G. Ariaans4, W. Dokter1
1Preclinical Department, 2Bio DSP, 3LEX Platform 4New Molecular Entities, Synthon Biopharmaceuticals BV, Nijmegen, The Netherlands
B. Weigmann, M. NeurathDepartment of Gastroenterology, Pneumology and Endocrinology of the Medizinische Klinik 1, Erlangen, Germany
B. CorthésyCentre Hospitalier Universitaire Vaudois, R & D Laboratory of the Division of Immunology and Allergy, Lausanne, Switzerland
Synthon 2
INTRODUCTION SECRETORY-IgA (SIgA)
SIgA produced in Lemna minor effectively binds human and mouse TNFα (Patent application WO2013/087912 )
Synthon
Cy5 labeled SIgA in greenZona Occludens (ZO-1) in red, Nuclei (DAPI) in blue
UPTAKE OF SIgA IN POLARIZED CACO-2 CELLS
Apical uptake of SIgA by polarized Caco-2 cells 3
Synthon
BIO-IMAGING OF ORALLY ADMINISTERED SIgA
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SIgA molecule ends up in gut, 24h after oral treatment
Synthon
LOCALIZATION OF SIgA IN DISTAL COLON AFTER TOPICAL ADMINISTRATION
SIgA localized in epithelial cells in distal colon after oral and rectal administration 5
Lumen SC-20656 ULEX-1 DAPI Lumen SC-20656 EpCAM DAPI
Sc-20656 (human secretory chain) in red, DAPI (Nuclei) in blue
LEFT ULEX-1 (Lectin) in green RIGHT EpCAM (Epithelial cell adhesion molecule) in green
Synthon
BIODISTRIBUTION (QWBA) SIgA IV AND PO
SIgA rapidly cleared from circulation after IV administration t1/2 ~2hVery low systemic exposure after oral administration 6
Intravenous
Oral
Caecu
m c
ontents
Large
inte
stin
e co
ntents
Smal
l inte
stin
e co
ntents
Stom
ach c
ontents
Urinar
y bla
dder: C
ontents
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200250300350400
ug
eq
uiv
ale
nts
/ g
1 hour2 hours
4 hours
8 hours24 hours48 hours72 hours
Bile (g
all b
ladder
)
Kidney
(whole
)
Liver
Lung
Lymph
Spleen
(whole
)
Urinar
y bla
dder c
ontents
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1 hour2 hours4 hours
8 hours24 hours48 hours72 hours
ug
eq
uiv
ale
nts
/ g
Synthon
SIgA IN TNBS-INDUCED IBD MODEL IN MICE
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SIgA inhibits TNBS-induced IBD after Oral and Rectal administration
Synthon 8
SUMMARY AND CONCLUSION
• We have successfully generated a monoclonal anti-TNFα secretory IgA antibody in duckweed.
• Anti-TNFα SIgA is a promising molecule for topical treatment of IBD, combining elimination of adverse effects associated with systemic exposure with the convenience of topical treatment.
SIgAs the future for topical IBD treatment!
