Blog: Immunogenicity Assessments – Frequently Asked Questions

02nd February 2024

Authors: CSO, Dr Campbell Bunce and VP of Research and Innovation, Dr Rob Holgate

Addressing the Complexities of Immunogenicity in Biologic Therapies 

Advanced therapies offer immense hope for treating complex diseases, yet they are often challenged by the body’s own defences through immunogenicity. This phenomenon, where the immune system identifies a drug as foreign, can significantly impact the effectiveness and safety of a treatment, diminish the drug’s efficacy, alter its pharmacokinetics, or even trigger autoimmune-like responses.  

Across Abzena’s development processes we have a commitment to understanding and managing immunogenicity to enhance the safety of all our products. For this reason, early prediction and mitigation strategies to reduce the risk of immunogenicity and its impact on drug efficacy and safety are integral to our approach to discovery, design and development. This not only serves to maximize the biologic’s efficacy and safety profile but also aligns with the rigorous immunogenicity assessments mandated by regulatory bodies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for biologic approval.  

Addressing immunogenicity concerns from the outset increases confidence in the likelihood of downstream success.Here we take a look at the frequently asked questions about immunogenicity assessments, drawing on information from our experts in the field. 

What is Immunogenicity? 

Immunogenicity refers to the ability of a substance, such as a therapeutic protein, to provoke an immune response. In the context of biologics, this response can impact both the efficacy and safety of the treatment. 

Why is Immunogenicity important in drug development? 

Immunogenicity is a key concern in developing biologics.  If a drug is immunogenic, anti-drug antibodies can be induced that bind to the drug and alter its efficacy and pharmacokinetic profile. In some cases, an autoimmune-like responses could be triggered. Anticipating and mitigating these responses early in the drug development process can significantly improve the likelihood of clinical success and patient safety, ensuring a smoother pathway to regulatory approval and market acceptance  

What are antibody-drug conjugates (ADCs) and their immunogenic risks? 

ADCs are targeted cancer therapies that link potent anti-cancer agents or other functional molecules to antibodies. As with any biologic-based therapeutic,  these can be immunogenic, leading to the production of antibody drug antigens (ADAs) that can reduce efficacy or cause adverse reactions. 

How do regulatory bodies view Immunogenicity? 

Regulatory agencies like the FDA and EMA require comprehensive immunogenicity risk assessments for the approval of biologics. Abzena’s expertise aligns with these regulatory standards, ensuring that our immunogenicity testing and management strategies meet global compliance requirements. These stringent requirements for immunogenicity risk assessment, ensure that potential issues are identified and addressed before clinical trials and market entry. 

What Role do Computational Tools Play? 

In silico tools, or computational methods, are pivotal in predicting immunogenicity risk. Using such algorithms to identify peptide sequences that may elicit an immune response helps guide the design and selection of therapeutic candidates with lower immunogenic potential. As these technologies are generally higher throughput and lower cost, they can be brought into the discovery and development process at a far earlier stage than in vitro assays, thereby effectively derisking projects.  

How Do In Vitro Methods Contribute to Immunogenicity Assessment? 

In silico platforms can be overly predictive, and so in vitro assays are crucial for evaluating the potential immunogenicity of biologics by providing real world empirical data to inform the drug development process. In vitro methods can also provide more flexibility by allowing different aspects of immunogenicity to be probed (mechanism of action, specific types of cell responses etc). Ultimately though, it is the synergy offered by using both in silico and in vitro approaches that provides the most comprehensive strategy for assessing immunogenic risk.  

What are the Immunogenicity Assessment Capabilities at Abzena? 

Abzena employs a combination of innovative technologies, regulatory knowledge, and a patient-centric approach to assess immunogenicity risks. We focus on developing phase-appropriate assays to assess potency, efficacy, and safety, ensuring informed decision-making throughout the drug development program. 

Abzena’s immunogenicity and safety assessment offering includes: 

  • Immunogenicity risk assessment of proteins using: 
  • Identification of immunogenic sequence “hot spots” using: 
    • In silico assessment by iTope-AI 
    • MHC Class II associated peptide proteomics (MAPPs) 
    • EpiscreenTM 2.0 T cell epitope mapping 
    • Pre-emptive molecule design and engineering to minimise “hot spots” 
  • Safety assessment of proteins with potential to induce cytokine storm using: 
    • Cytokine Release Assay 

Abzena offers tailored solutions for each stage of your drug development journey. Our approach encompasses the development of phase-appropriate assays for potency, efficacy, and safety, ensuring that you have the necessary tools to make informed decisions. Our comprehensive suite of services includes target validation, mode of action analysis, and immunogenicity and safety assessment, among others.

From discovery through manufacturing, Abzena’s services are designed to meet your specific requirements, ensuring high-quality data that informs strategic decision-making. Find out more about how Abzena’s bespoke immunogenicity assay strategies can streamline your path from laboratory to therapeutic.