ANTI-DRUG ANTIBODIES

Need to monitor of your antibody drug? Trust ProteoGenix experts for the development of your PK/PD and immunogenicity assays. With the best antibody production technologies on board and 1800+ antibodies produced, we provide the best guarantees to get high sensitivity and specificity anti-drug antibodies.

What is an anti-drug antibody?

An anti-drug antibody refers to an antibody binding to the idiotope of another antibody, generally an antibody drug. An idiotope corresponds to a region within the Fv region binding to the paratope of a different antibody.

Anti-idiotypic antibodies against therapeutic antibodies can be generated for various applications such as PK/PD studies or immunogenicity studies. They can be divided into 3 different types and are particularly useful for the quantification of specific antibody drugs:

• Antigen blocking anti-idiotype antibodies: this type of anti-idiotypic antibodies is paratope specific meaning that antibodies idiotope and paratope overlap with one another. Therefore, the target antigen and the anti-idiotypic antibody compete for the same binding site. These antibodies are commonly used for free antibody drug measurement.
• Non-blocking anti-idiotypic antibodies: this type of anti-idiotypic antibodies is characterized by an antibody drug binding outside of the antigen binding site (antibodies idiotope and paratope do not overlap). These antibodies are used for total antibody drug detection and quantification.
• Complex specific anti-idiotypic antibodies: complex specific anti-idiotypic antibodies bind only to the antibody-drug antigen complex. Therefore, they are typically used to quantify bound antibody drug in a sample.

As an antibody development expert, ProteoGenix offers all types of highly specific and sensitive anti-idiotypic antibodies. To get more information about our service, contact our dedicated account manager.

Anti-drug antibodies for preclinical and clinical applications

Anti-drug antibodies are commonly used for detection and quantification of therapeutic antibodies during the drug development process. One of the major challenges encountered in this type of measurement comes from the complex composition of the serum as the human serum is composed of a high excess of human antibodies. Thus, there is a high degree of similarity between the endogenous human antibodies and the humanized or fully human antibody drug. Therefore, highly specific and highly sensitive antibodies are a prerequisite to perform reliable pharmacokinetic and immunogenicity assays.

Pharmacokinetic Assays

Pharmacokinetic assays are commonly based on ligand binding assays for the quantification of various forms of monoclonal antibody drugs (free, bound, total). The accuracy of the designed assay is of primary importance for the assessment of the exposure-response relationship in order to determine the optimal dose and safety parameters.

Generation of anti-idiotypic antibodies offers a more accurate quantification in comparison with the use of generic assays based on less specific antibodies such as light-chain antibodies. The latter can be used at the preclinical phase as a first total mAb approximation but could no longer be used on clinical samples.

Several ELISA assays exploiting anti-drug antibodies are commonly used to quantify the different forms of therapeutic antibodies in pharmacokinetic assays. Here are some examples of the design commonly used.

Immunogenicity Assays

Immunogenicity represents the ability of an antibody drug to generate an immune response. When the immune response is directed against a therapeutic antibody (antibody-drug antibodies, ADA), it can dramatically impact the antibody drug efficacy and safety. Thanks to their ability to bind specifically to an antibody drug, anti-drug antibodies and anti-idiotypic antibodies share a common property. Thus, polyclonal as well as monoclonal anti-idiotypic antibodies can be used as a reference for immunogenicity assays.