Research: Exploring the Spatial Proximity Analyte Reagent Capture Luminescence (SPARCL) Assay as a New Modality for Evaluating Mouse Anti-Human Antibody (MAHA)
Mentor: Tyler Weisbarth
Awards: Somers Science Fair 2022- 3rd place in Medicine and Health, WESEF 2024 - Visionary Engineering Award, Science Talent Search participant, Junior Science and Humanities Symposium participant.
Research Location: Regeneron Pharmaceuticals
Abstract:
Mouse anti-human antibody (MAHA) is an anti-drug antibody (ADA) response that is elicited when a human antibody enters a mouse. This rapid clearance can confound the pharmacokinetic profiles of dosed drugs in clinical trials, and as such, MAHA titers must be measured. The current enzyme-linked immunosorbent assay (ELISA) requires three days of labor, while the proposed spatial proximity reagent capture luminescence (SPARCL) assay requires one day. To assess the differences in benefits of ELISA and SPARCL, the MAHA assay was run on both platforms. Wild-type and humanized mice were dosed with either an isotype control that would not elicit MAHA or a drug known to elicit MAHA. Serum samples were taken at regular time points. Antibody concentrations were obtained using a GyroLab Immunoassay. Pharmacokinetic profiles were analyzed using Prism software. Antibody concentration profiles were indicative of MAHA for the drug group but not the control group. SPARCL was able to detect MAHA titers in the drug group, while the assay determined no MAHA titers in the control groups. SPARCL could detect MAHA in both the humanized and wild-type mice. A comparison between ELISA and SPARCL titers showed that SPARCL yielded consistently lower titers but followed a similar trend to the ELISA. This may be because the ELISA measures some background noise in the absence of a dosed antibody, while SPARCL is suspected to be a cleaner assay. SPARCL is a viable assay platform to run the MAHA assay but SPARCL requires further optimization to adequately replace ELISA in pharmacokinetic studies.
About this Scientist:
Penelope “Penny” Cloonan is a senior who is currently pursuing her IB Diploma at Yonkers High School. She will be attending Case Western Reserve University as a biochemistry major in the fall. After college, she plans on earning her M.D. to become a practicing gynecologist.
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