Research: Exploring New Modalities for Evaluating MAHA
Awards: Somers Science Fair 2022 - 2nd place Medicine and Health
Mentor: Tyler Weisbarth
Research Location: Regeneron
Abstract:
Anti-drug antibody (ADA) responses peak when a foreign substance enters an organism. In order to assess the impact of ADA responses, isotype controls are used. This rapid clearance of foreign substances – in clinical trials drugs – can confound the pharmacokinetic profiles of dosed drugs in clinical trials. Pharmacokinetic profiles are further confounded when there is variation in the isotype control. Wild-type and humanized mice were dosed with either a known ADA response, and the currently used isotype control (CUI), mouse anti-human antibody-causing drug (MAHA), or the proposed isotype control (PIC). Blood samples were taken at multiple time points and were in turn used for the MAHA assay. Antibody titers were obtained via an enzyme-linked immunosorbent assay (ELISA), and protein concentrations were obtained using a GyroLab Immunoassay. Pharmacokinetic profiles were analyzed using Prism software. The titers confirmed that there was evidence of MAHA in the drug group and not in the isotype control groups. The isotype controls both behaved consistently in the wild-type mice. The CUI behaved inconsistently in the humanized mice which is problematic because there was no target on board that should cause that reaction. The PIC behaved consistently in the humanized mice, suggesting potential as a viable isotype control. In both the wild-type and humanized mice group, the isotype controls showed comparable titers. The PIC has potential as a new isotype control however it has limited use in that the PIC is only available in 2 of the 4 classes that the CUI is available in.
About this Scientist:
Penelope Cloonan is a junior at Yonkers High School. She first became enamored with science by watching mad scientists in her favorite superhero shows, but she promises to use her knowledge for good. Penelope is currently researching ways to improve pharmacokinetic assays involving antibodies and hopes to one day apply this knowledge to a future career in gynecology.