Extreme drug-tolerance in immunogenicity testing

Immunogenicity describes an immune response caused by a foreign biological substance. While vaccines intend to create such a response, it is unwanted when directed against a therapeutic drug. Large molecule drugs, such as therapeutic antibodies, peptides or proteins, can be recognized by the patient’s immune system and elicit the production of anti-drug-antibodies (ADAs). As they can adversely affect the pharmacokinetics, pharmacodynamics, safety, and efficacy of the therapeutic agent, ADA formation is a great challenge in biological drug development.

ADAs might bind to therapeutic proteins and affect their efficiency and clearance. They could also cross-react to endogenous proteins and induce downstream effects that range from mild side effects, allergic reactions, altered pharmacokinetics up to severe effects on patient health.


 

Immune reactions are complex and responses can occur in a range between clinically not noticalble and life-threatening. We develop your assay tailored to your drug and disease and support your study before, during and after approval, since a routine monitoring can show drug efficiancy reduction after longer time periods.

 

 


The extend of anti-drug-antibody formation can be dependent on the individual patient, type of administration or the biological molecule itself. Thus, an understanding of potential immune responses is crucial.

High drug concentrations, due to high-level dosing or long half-life, can complicate ADA detection - especially in ADA-bridging assays, where labeled drug conjugates and free drug are competing for ADAs. In such cases, breaking up drug-ADA-complexes can optimize drug tolerance.

Development of valid and selective assays to measure ADA responses is a key aspect of therapeutic protein product development. An assessment of immunogenicity is dependent on key operating parameters of the assays: sensitivity (detection of clinically relevant levels of ADAs), specificity (interference of on-board drug, matrix), and NAbs (potentially blocking the efficacy of the biotherapeutic).

High drug concentrations, due to high-level dosing or long half-life, can complicate anti-drug antibody detection - especially in ADA-bridging assays, where labeled drug conjugates and free drug are competing for ADAs. Our team is highly experienced in the development of immunoassays that ensure immunogenicity testing with extreme drug tolerance.

Chimera Biotec supports assays from preclinical immunogenicity studies to clinical trials.

     • Anti-drug antibodies (ADA)

     • Neutralizing antibodies (NAb)


Multi-tiered approach for ADA assessment

  • Screening assay
    • Sensitive assay that detects low- and high- affinity anti-drug antibodies within the clinical sample. Reactive samples will be evaluated in a subsequent confirmatory assay.
  • Confirmatory assay
    • A competition assay that confirms specific binding of ADA to the therapeutic protein of interest. Eliminates potential false-positive results from unspecific binding events in the initial screening assay. ADA-confirmed samples will be characterized in a subsequent titering or neutralizing assay.
  • Titration assay
    • Characterize the magnitude of the ADA response
  • Neutralizing assay
    • Asses ADA for neutralizing activity

Anti-drug antibody detection that match your unique study needs

Chimera develops ADA and Nab assays with highest sensitivity, specificity and selectivity for your therapeutic protein. All assay can be validated in compliance with GLP/GCP-regulations to support studies from pre-clinical drug development to clinical studies.
 

Most suitable platform for your immunogenicity assay

MSD-ECL is the gold standard for immunogenicity testing in human samples for most studies. Based on your specific study requirements our scientists will develop and validate an assay on our ELISA, MSD-ECL or Immuno-PCR platform (all compliant to GLP/GCP).


Chimeras features in Immunogenicity testing services

  • Full assay development and validation
  • Compliant to GLP and GCP
  • Study support from preclinic to clinic
  • Multiple platforms available

For guidance reference see FDA: Immunogenicity Testing of Therapeutic Protein Products — Developing and Validating Assays for Anti-Drug Antibody Detection (2019) or EMA: Guideline on Immunogenicity assessment of therapeutic proteins (2017)

 

Our ADA and NAb assays are based on the MSD™ technology.

Trade off immunoassay sensitivity for optimized drug-tolerance in immunogenicity testing.

 

Immunogenicity literature list