Immunogenicity Analysis of ADCs

Immunogenicity testing is an important component of clinical development for large-molecule biotherapeutics. For novel therapies such as antibody-drug conjugates (ADCs), the unique structural components may contribute additional complexities to both immunologic responses and bioanalytical methods. To help our clients meet the bioanalytical and immunogenicity challenges of ADCs, Creative Proteomics has established a comprehensive platform for the immunogenicity analysis of ADCs, equipped with a variety of advanced technologies. Our experts have extensive expertise in ligand binding and liquid chromatography-mass spectrometry to help support our customers in the immunogenicity assessment of ADCs throughout the drug development process.

Introduction to The Immunogenicity of ADCs

As with all biological agents, ADCs have the potential to induce an immune response. This may include antibodies involving multiple ADC components, linkers, drugs, or epitopes (anti-therapeutic antibodies). In addition to being immunogenic like all biological agents, ADCs have unique features, such as ADC molecules or ADC fragments with drug molecules that bind to ATA to create unique immune complexes that may deliver cytotoxic drugs to unintended locations. Therefore, the immunogenicity of ADCs needs to be carefully evaluated.

Our ADCs Immunogenicity Assessment Services

Immunogenicity assessment services for antibody drug conjugates provided by Creative Proteomics typically utilize a multi-tiered testing approach, which includes anti-drug antibody (ADA) screening and confirmation, antibody titer testing, neutralizing antibody testing, and antibody subtyping. If the results of screening and confirmatory assays indicate the presence of an antibody response, we then decide whether to conduct further preclinical studies of the antibody response, such as antibody titer, positive rate of antibody response, and whether it is a neutralizing antibody, based on the necessity and the purpose of the research and development. At Creative Proteomics, we typically perform immunogenicity testing in conjunction with repeat dosing toxicity studies and collect blood samples at different time points during the dosing and recovery periods to obtain rigorous immunogenicity data.

• Anti-drug antibody (ADA) screening and confirmation

ADCs may become immunogenic in the human body, causing the body to produce anti-therapeutic antibody (ATA). In general, ADAs elicited for an ADC includes those specific to intact ADC, to linker, to payload, and to the unconjugated antibody. Creative Proteomics utilizes our LBA platform and LBA-LC-MS/MS platform to correctly detect all ADAs generated against ADCs, specifically identifying the presence or absence of antibodies against the drug. By accurately characterizing ADAs, we can assess the immune response that may be triggered by antibody drug conjugates.

• Antibody titer assay

We also offer antibody titer assays to quantify the concentration of ADA in a sample. This quantitative analysis helps to determine the incidence and extent of ADA response to a drug. Long-term monitoring of ADA titers allows for effective assessment of the associated immunogenicity risk.

• Neutralizing antibody assay

Our neutralizing antibody assays are designed to assess the ability of ADA to inhibit the pharmacological activity of ADCs. Our advanced assay technology allows us to quantitatively assess the neutralizing potential of ADA, helping our customers to improve and optimize drug efficacy.

• Antibody subtype analysis

Antibody subtype analysis helps determine the specificity of ADA. Our analytical services help clients identify the subtypes of antibodies that respond to their ADCs, providing information on drug efficacy and safety.

Our Immunogenicity Assessment Methods

Creative Proteomics offers a variety of methods for immunogenicity assays of ADCs, including but not limited to:

• Enzyme Linked Immunoassay (ELISA)
• Radioimmunoassay (RIA)
• Biofilm Interferometry (BLI)
• Surface plasmon resonance (SPR)
• Electrochemiluminescence (ECL)

Different combinations of methods can be used to characterize the response of anti-ADC antibodies and help researchers make informed decisions in the development and use of antibody drug conjugates.

Advantages of Our ADCs Immunogenicity Assessment Services

• Customized assay protocols and multiple assay formats.
• Development and validation of cell-based assays, receptor binding assays, or competitive ligand binding assays for the detection of neutralizing antibodies.
• Analysis of ADA results combined with pharmacological and/or toxicological changes to provide clients with a comprehensive analytical report.

Creative Proteomics' experts work closely with you and aim to provide accurate, reliable and comprehensive immunogenicity assessment services for antibody drug conjugates to support your drug development process. Contact us to learn more about our service and we will be happy to serve you.