期刊
MABS
卷 14, 期 1, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/19420862.2022.2104153
关键词
Monoclonal antibody; antibody generation; target engagement; TE; biomarker; IL-11; bioanalytical assay; SPR; PK; PD; modeling; mechanistic modeling; antibody therapeutic; SP-X; MSD; simoa
An in-house antibody generation campaign successfully developed a novel ultra-sensitive target engagement assay for IL-11 and established baseline levels of IL-11. This has significant implications for drug development and preclinical research.
An in-house antibody generation campaign identified a diverse, high affinity set of anti-interleukin-11 (IL-11) monoclonal antibodies (mAbs) to enable successful development of novel, custom ultra-sensitive target engagement assays for detection of free (unbound to the dosed anti-IL-11 therapeutic mAb) and total (free and mAb-IL-11 complexed form) IL-11 in preclinical species and human. Antibody hits from distinct epitope communities were screened on various platforms, including enzyme-linked immunosorbent assay, Meso Scale Discovery, Simoa HD-1 and Simoa Planar Array (SP-X), and used for assay development and sensitivity optimization. The ultra-sensitive SP-X format achieved a lower limit of quantitation of 0.006 pg/mL, enabling the first reported baseline levels of IL-11 in healthy control plasma determined by custom bioanalytical assays. These newly established baseline levels supported mechanistic pharmacokinetic/pharmacodynamic modeling in mouse, cynomolgus monkey, and human for a greater understanding of preclinical study design and in vivo dynamic interaction of soluble IL-11 with an anti-IL-11 antibody therapeutic candidate. Modeling and simulation also helped refine the utility of assays with respect to their potential use as target engagement biomarkers in the clinic.
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