Allergy Asthma Immunol Res.  2019 Mar;11(2):291-298. 10.4168/aair.2019.11.2.291.

Higher Binding Affinity and In Vitro Potency of Reslizumab for Interleukin-5 Compared With Mepolizumab

Affiliations
  • 1R&D, Biologics Lead Antibody Discovery, Teva Pharmaceuticals Australia, Sydney, NSW, Australia. mark.liddament@tevapharm.com
  • 2R&D, Biologics, Teva Pharmaceuticals USA, West Chester, PA, USA.

Abstract

Reslizumab and mepolizumab are recently approved monoclonal antibodies for the treatment of severe (uncontrolled) eosinophilic asthma. Both are effective in neutralizing the function of interleukin-5 (IL-5). This study is the first to compare the binding affinity and in vitro potency of both antibodies in head-to-head assays. Two assays assessed binding affinity (using the equilibrium dissociation constant [K(D)]) of each drug for human IL-5. In the Biacore surface plasmon resonance assay, the association constant (k(on)) values for human IL-5 for reslizumab and mepolizumab were 3.93 × 10⁶ and 1.83 × 10⁵, respectively. The dissociation constant (k(off)) values were 4.29 × 10⁻⁴ and 2.14 × 10⁻⁴, respectively. Calculated K(D) values for human IL-5 for reslizumab and mepolizumab were 109 and 1,170 pM, respectively, representing an approximately 11-fold stronger binding affinity with reslizumab. In the Kinetic Exclusion Assay, the k(on) values for human IL-5 for reslizumab and mepolizumab were 3.17 × 10⁶ and 1.32 × 10⁵, respectively. The k(off) values were 1.36 × 10⁻⁵ and 1.48 × 10⁻⁵, respectively. Measured K(D) values for human IL-5 for reslizumab and mepolizumab were 4.3 and 112 pM, respectively, representing an approximately 26-fold stronger binding affinity for reslizumab. A human-IL-5-dependent cell proliferation assay was developed to assess in vitro potency, based on a human cell line selected for enhanced surface expression of IL-5 receptor-alpha and consistent proliferation response to IL-5. The concentration at which 50% inhibition occurred (IC₅₀) was determined for both antibodies. Reslizumab and mepolizumab inhibited IL-5-dependent cell proliferation, with IC₅₀ values of approximately 91.1 and 286.5 pM, respectively, representing on average 3.1-fold higher potency with reslizumab. In conclusion, comparative assays show that reslizumab has higher affinity binding for and in vitro potency against human IL-5 compared with mepolizumab. However, these results do not take into consideration the different methods of administration of reslizumab and mepolizumab.

Keyword

Reslizumab; mepolizumab; antibody affinity; interleukin-5; drug evaluation, preclinical

MeSH Terms

Antibodies
Antibodies, Monoclonal
Antibody Affinity
Asthma
Cell Line
Cell Proliferation
Drug Evaluation, Preclinical
Eosinophils
Humans
In Vitro Techniques*
Interleukin-5*
Surface Plasmon Resonance
Antibodies
Antibodies, Monoclonal
Interleukin-5
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