Anti-IgG Fc monoclonal antibody [DyLight® 488]

Purpose The aim of this work was to identify whether biochemical and physiological sources of mAb pharmacokinetic sex-effects could be identified in the rat model where target-mediated disposition is avoided. Methods Plasma and lymphatic pharmacokinetics of the humanised anti-EGFR antibody cetuximab, along with potential physiological and biochemical drivers of pharmacokinetic sex differences, were examined in male and female rats. Cetuximab was used as a model mAb since plasma clearance is slower in female patients. Results When plasma concentrations were normalised to dose, female rats displayed slower plasma clearance than males, but no significant differences were observed in liver and spleen biodistribution. Sex differences in apparent plasma clearance, however, were abolished after normalisation to body weight, surface area or fat-free mass. Significant sex differences were observed in plasma testosterone, endogenous IgG and fat free mass, but did not correlate with apparent clearance. Females did, however, show two-fold higher lymphatic exposure compared to males. Conclusions These data suggested that mAbs more efficiently access lymph in females, but this does not affect plasma pharmacokinetics or biodistribution. Further, the data suggest that sex differences observed in humans could be a function of antigen density.

Compact multiplexed biosensors systems hold great potential for diagnosis of diseases where the detection of multiple biomarkers is required. Hypersensitivity Immunoglobulin E mediated syndromes are primary immunodeficiency disorders associated with sensitization to allergens. Assessing immunoglobulin E (IgE) sensitization to allergens is an important strategy for allergy diagnosis. Here, we report for the first time a reliable, flexible and cost-effective optoelectrical biosensor system for the simultaneous determination of total and allergen-specific IgE and IgG, antibodies using an immunogold-silver signal amplification method. The biosensor was constructed on a regular digital versatile disc (DVD) to immobilize a panel of 12 allergen extracts or pure proteins in microarray format, as a proof of concept. The multiplexed biosensor showed a limit of detection of 0.26 IU/mL (624 pg/mL) and 14 ng/mL for IgE and IgG antibodies, respectively. The system was successfully applied in a cohort of 127 human serum samples, showing good sensitivity (97.6%) as well as specificity (85.7%), and an excellent area under the curve (AUC) value was found at 0.977 (confidence interval, CI 0.957 to 0.990) as compared and validated with a reference clinical immunofluorescence assay, confirming an excellent correlation between both techniques. The multiplex biosensor system with on-demand panel composition can be used fully autonomously in clinical or mobile laboratory settings without the need for any additional medical equipment, with which could make it suitable for massive allergy screening campaigns to better define sensitization profiles.