Anti-drug antibodies produced by biological therapeutics often affect drug pharmacodynamics, pharmacokinetics, efficacy, and patient safety. Hence, immunogenicity testing becomes crucial to evaluate the potential of a biotherapeutic in producing anti-drug antibodies (ADA). Anti-drug antibodies can neutralize or non-neutralize, making them critical, especially in clinical drug development.
Today, multiple immunogenicity assay formats are available, including ELISA, surface plasmon resonance, electrochemiluminescence-based assays, and radioimmunoassays. Out of these assays, ELISA and Meso Scale Discovery platforms are employed widely in immunogenicity assays. However, identifying the neutralizing ability of anti-drug antibodies is crucial. Hence, bioanalysis services heavily focus on neutralizing antibody (NAb) assay to confirm the neutralizing capacity of ADAs.
The current article reviews emerging techniques and applications in the space of ADA assay.
Gyrolab platform
The gyrolab platform is a widely employed bioanalytical technique and ligand binding assay format. This tool employs microfluidics with partial automation to quantify several biological drug candidates and determine their protein-protein interaction and pharmacokinetic properties.
Due to its microfluidic nature, the gyrolab technique uses minimal sample volumes and critical reagents. For the gyrolab platform using the ADA mixing CD, researchers can keep the runtime less than 1 hour. However, this relatively short incubation period for bridging and neutralization reactions may not be enough for low-affinity antibodies to develop a bridged complex. Researchers can resolve this challenge by optimizing the incubation period for the neutralization and bridging steps during the development process.
iPCR immunogenicity assay
Interference caused by circulating drugs is a significant obstacle associated with methodology for anti-drug antibody testing. Processes such as ADA enrichment and acid dissociation have proven successful in improving drug tolerance. Besides, samples are collected after a washout session to improve drug tolerance. One approach to enhance drug tolerance is by having a large number of dilutions to minimize drug concentrations in the sample. Techniques such as immune PCR (iPCR) have high sensitivity that may allow anti-drug antibody detection in such diluted samples.
In addition to enhanced drug tolerance, iPCR allows large sample dilution and hence reduces matrix effects. However, researchers should consider multiple aspects, such as the need for proprietary reagents and rigorous analyst training, while implementing iPCR assays for immunogenicity testing.
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SQI squid lite technology
Often, researchers require new assays to isotype anti-drug antibodies and characterize immune responses. The SQI diagnostic squid lite platform has the option of isotyping and detecting anti-drug antibodies in the same assay well. This feature eliminates the requirement for multiple assays and reduces the total amount of sample volumes.
Several research studies have reported enhanced drug tolerance and sensitivity using squid lite technology compared to the ECL or ELISA platform. The primary advantage of this technology is multiplexing capacities when isotyping is required. Besides, the automated system increases assay reports. However, researchers should consider experimental aspects of SQI technology, such as proprietary buffers and substantial upfront investment.
In Conclusion
Identifying the presence of anti-drug antibodies and determining their neutralizing antibodies is crucial for generating safe and reliable biotherapeutics. Hence, developing robust immunogenicity assays remains critical for the successful development of biotherapeutics.