Eric Escobar-Cabrera

Dr. Eric Escobar-Cabrera


Research Focus & Metrics

Academic Career Length

10Years (2017-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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16 May 2017 in Antibodies
Verified
Journal Article
Open access
PDF file
EEEric Escobar-Cabrera
Eric Escobar-Cabrera
PLPaula Lario
Paula Lario
JBJason Baardsnes
Jason Baardsnes
JSJoseph Schrag
Joseph Schrag
YDYves Durocher
Yves Durocher
SDSurjit Dixit
Surjit Dixit
Asymmetric bispecific antibodies are a rapidly expanding therapeutic antibody class, designed to recognize two different target epitopes concurrently to achieve novel functions not available with normal antibodies. Many therapeutic designs require antibodies with reduced or silenced effector function. Although many solutions have been described in the literature to knockout effector function, to date all of them have involved the use of a specific antibody subtype (e.g., IgG2 or IgG4), or symmetric mutations in the lower hinge or CH2 domain of traditional homodimeric monospecific antibodies. In the context of a heterodimeric Fc, we describe novel asymmetric Fc mutations with reduced or silenced effector function in this article. These heteromultimeric designs contain asymmetric charged mutations in the lower hinge and the CH2 domain of the Fc. Surface plasmon resonance showed that the designed mutations display much reduced binding to all of the Fc gamma receptors and C1q. Ex vivo ADCC and CDC assays showed a consistent reduction in activity. Differential scanning calorimetry showed increased thermal stability for some of the designs. Finally, the asymmetric nature of the introduced charged mutations allowed for separation of homodimeric impurities by ion exchange chromatography, providing, as an added benefit, a purification strategy for the production of bispecific antibodies with reduced or silenced effector function.