Immunogenicity testing, a crucial step
Immunogenicity risk assessment is a crucial step in the development of therapeutic drug products. These assays are important because they allow us to understand the anti-drug antibody response to a patient's immune system which in turn helps us understand its safety and efficacy.
KCAS Bio has experience in assessing immunogenicity in a wide range of Biologics:
- Monoclonal Antibodies
- Antibody Fragments
- Antibody Drug Conjugates (ADCs)
- Fusion Proteins
- Gene Therapies
Immunogenicity assay development
KCAS Bio has a large (>60+ FTEs) ligand binding assay team that has 100s of years of combined experience with developing a wide range of immunogenicity assays from ADAs to cell based NAbs. Using a multitiered approach, KCAS Bio can customize your assay depending on your study requirements, through all phases of development.
Tools to overcome immunogenicity challenges
Immunogenicity assays do not follow a one size fits all approach. We have the expertise to overcome challenges in immunogenicity assays caused by high background or insufficient drug tolerance starting at the experimental design, through method development/validation and into bioanalysis. Our team of scientists understand these challenges and have overcome them using a variety of techniques.
The most common assay formats are:
- Acid Dissociation
- Affinity Capture and Elution (ACE)
- Solid Phase Extraction and Acid Dissociation (SPEAD)
Acid dissociation is a widely used method for improving drug tolerance in an assay. When a weak acid is added to a sample it dissociates the drug: antibody complex. Once the sample is neutralized the ADA can bind to the biotinylated drug forming a bridge, this allows for the detection of the ADA. At KCAS Bio, we frequently add MgCl2 to help facilitate the breaking up of immune complexes.
Affinity Capture and Elution (ACE)
Affinity capture elution (ACE) is a method used in detecting ADA to increase the assay drug tolerance. The method uses acid disassociation of ADA-therapeutic interaction. This allows for preferential capture of ADA by an immobilized version of the dosed therapeutic. A second dissociation step is used to enable selective transfer of treated sample to an MSD bridging assay. Following the ACE procedure this assay utilizes biotinylated and ruthenium labeled drug to detect anti-drug antibodies.
Solid Phase Extraction & Acid Dissociation (SPEAD)
Solid Phase Extraction and Acid Dissociation (SPEAD) is a plate-based method for reducing drug interference in the ADA assay. This method uses weak acids to dissociate the drug: antibody complex. The sample is neutralized and binds a biotinylated drug which is then captured on the streptavidin-coated 96 well plate. After the plate is washed, a second acid treatment is used to elute the ADA bound to the plate. The sample containing the ADA is transferred, neutralized, followed by incubation with the labeled drug to form a bridge which is detected using ECL.
Statistical support for calculating cut points in immunogenicity testing
Interpreting results from Immunogenicity testing per guidelines can be challenging. We utilize the Red Thread™ module for Immunogenicity/Anti-drug Antibody (ADA) cut-point analysis. The Red Thread™ module uses the power of expert systems to simplify and automate the tedious, time-intensive and complicated process of analyzing cut-points for ADA studies.
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