Abstract
The aim of this study was, at the assay development stage and thus with an appropriate degree of rigor, to select the most appropriate technology platform and sample pretreatment procedure for a clinical ADA assay. Thus, ELISA, MSD, Gyrolab, and AlphaLISA immunoassay platforms were evaluated in association with target depletion and acid dissociation sample pretreatment steps. An acid dissociation step successfully improved the drug tolerance for all 4 technology platforms and the required drug tolerance was achieved with the Gyrolab and MSD platforms. The target tolerance was shown to be better for the ELISA format, where an acid dissociation treatment step alone was sufficient to achieve the desired target tolerance. However, inclusion of a target depletion step in conjunction with the acid treatment raised the target tolerance to the desired level for all of the technologies. A higher sensitivity was observed for the MSD and Gyrolab assays and the ELISA, MSD, and Gyrolab all displayed acceptable interdonor variability. This study highlights the usefulness of evaluating the performance of different assay platforms at an early stage in the assay development process to aid in the selection of the best fit-for-purpose technology platform and sample pretreatment steps.
Highlights
Monoclonal antibodies have been successfully used as therapeutic agents for the treatment of diseases including breast cancer, leukemia, asthma, arthritis, psoriasis, Crohn’s disease, and transplant rejection [1,2,3,4,5]
We describe the development of an anti-drug antibody (ADA) assay for a therapeutic antibody directed against a soluble dimeric target (Novimab) with evaluation of different technology platforms (ELISA, MSD, Gyrolab, and AlphaLISA) and different additional steps (±acid dissociation, ±target depletion) in order to achieve an assay with an appropriate sensitivity, drug tolerance, and target tolerance for our clinical trial population
The aim of this study was to develop an ADA assay on different technology platforms (ELISA, MSD, Gyrolab, and AlphaLISA) with different additional steps (±acid dissociation, ±target depletion) in order to achieve an assay with an appropriate sensitivity, interdonor variability, drug, and target tolerance level
Summary
Monoclonal antibodies have been successfully used as therapeutic agents for the treatment of diseases including breast cancer, leukemia, asthma, arthritis, psoriasis, Crohn’s disease, and transplant rejection [1,2,3,4,5]. As part of a therapeutic antibody clinical development program it is necessary to evaluate the immunogenic potential of the antibody. This is measured as an anti-drug antibody (ADA) response and if it occurs it can cause undesired effects ranging from loss of drug exposure and loss of efficacy to serious adverse events. The samples are initially screened for their ability to bind the therapeutic drug, screened positive samples are confirmed in a second assay, and their isotype and neutralizing capacity can be evaluated. New immunoassay platforms have been developed including MSD, Gyrolab, and AlphaLISA with improved sensitivity, accuracy, variability, reduced assay time, and reduced sample volume requirements
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