Physical characterization and in vitro biological impact of highly aggregated antibodies separated into size-enriched populations by fluorescence-activated cell sorting

Journal of Pharmaceutical Sciences
Srivalli TelikepalliDavid B Volkin

Abstract

An IgG2 monoclonal antibody (mAb) solution was subjected to stirring, generating high concentrations of nanometer and subvisible particles, which were then successfully size-enriched into different size bins by low-speed centrifugation or a combination of gravitational sedimentation and fluorescence-activated cell sorting (FACS). The size-fractionated mAb particles were assessed for their ability to elicit the release of cytokines from a population of donor-derived human peripheral blood mononuclear cells (PBMC) at two phases of the immune response. Fractions enriched in nanometer-sized particles showed a lower response than those enriched in micron-sized particles in this assay. Particles of 5-10 μm in size displayed elevated cytokine release profiles compared with other size ranges. Stir-stressed mAb particles had amorphous morphology, contained protein with partially altered secondary structure, elevated surface hydrophobicity (compared with controls), and trace levels of elemental fluorine. FACS size-enriched the mAb particle samples, yet did not notably alter the overall morphology or composition of particles as measured by microflow imaging, transmission electron microscopy, and scanning electron microscopy-energy dispers...Continue Reading

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Citations

Feb 13, 2016·Journal of Pharmaceutical Sciences·Ehab M MoussaElizabeth M Topp
Apr 6, 2016·Journal of Pharmaceutical Sciences·Wim JiskootLinda O Narhi
Jul 3, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Kirsty D RatanjiJeremy P Derrick
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May 31, 2017·Frontiers in Immunology·Marc J PallardyArmelle Biola-Vidamment
Sep 30, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Myriam NabhanUNKNOWN ABIRISK Consortium
Sep 30, 2019·Journal of Pharmaceutical Sciences·Lorenzo GentiluomoWolfgang Frieß

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