Design and characterization of Zweimab and Doppelmab, high affinity dual antagonistic anti-TSLP/IL13 bispecific antibodies

Patients with severe Th2 type asthma often have a steroid resistant phenotype and are prone to acute exacerbations. Current novel therapies have only marginal therapeutic effects. One of the hypotheses for lack of major efficacy in most patients is targeting only one redundant pathway leaving others...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2018-09, Vol.504 (1), p.19-24
Main Authors: Venkataramani, Sathyadevi, Low, Sarah, Weigle, Bernd, Dutcher, Darrin, Jerath, Kavita, Menzenski, Monica, Frego, Lee, Truncali, Kris, Gupta, Pankaj, Kroe-Barrett, Rachel, Ganesan, Rajkumar, Singh, Sanjaya, Erb, Klaus J.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
ANTIBODIES
ASTHMA
Bispecific
Epitope mapping
IL13
LYMPHOKINES
PHENOTYPE
SPR
STEROIDS
TSLP
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Summary:Patients with severe Th2 type asthma often have a steroid resistant phenotype and are prone to acute exacerbations. Current novel therapies have only marginal therapeutic effects. One of the hypotheses for lack of major efficacy in most patients is targeting only one redundant pathway leaving others active. Hence, we have designed and developed novel highly potent bispecific anti-TSLP/IL13 antibodies called Zweimabs (monovalent bispecific) and Doppelmabs (bivalent bispecific) that concurrently inhibits the signaling by these two cytokines. •Lack of efficacy from anti-IL13 monotherapies.•Dual targeting TSLP and IL13 due to great overlap of signaling pathways.•Design and development of Zweimab and Doppelmab bispecifics targeting TSLP and IL13.•Zweimabs and Doppelmabs are highly potent with picomolar affinity to the targets.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2018.08.064