%0 Journal Article
%T Higher Binding Affinity and In Vitro Potency of Reslizumab for Interleukin-5 Compared With Mepolizumab
%A Adam W. Clarke
%A Anthony Doyle
%A David Laine
%A David Mabon
%A Jacquelyn Lyons
%A Jean Husten
%A Laurie Pukac
%A Mark Liddament
%A Tanya Estephan
%J Archive of "Allergy, Asthma & Immunology Research".
%D 2019
%R 10.4168/aair.2019.11.2.291
%X 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 [KD]) of each drug for human IL-5. In the Biacore surface plasmon resonance assay, the association constant (kon) values for human IL-5 for reslizumab and mepolizumab were 3.93 ¡Á 106 and 1.83 ¡Á 105, respectively. The dissociation constant (koff) values were 4.29 ¡Á 10£¿4 and 2.14 ¡Á 10£¿4, respectively. Calculated KD 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 kon values for human IL-5 for reslizumab and mepolizumab were 3.17 ¡Á 106 and 1.32 ¡Á 105, respectively. The koff values were 1.36 ¡Á 10£¿5 and 1.48 ¡Á 10£¿5, respectively. Measured KD 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
%K Reslizumab
%K mepolizumab
%K antibody affinity
%K interleukin-5
%K drug evaluation
%K preclinical
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340799/