The advent of recombinant technology leads to revolutionary novel methods of drug development that allow the production of any protein-based drug in cell culture. These protein-based biopharmaceuticals have some important advantages, such as longer half-lives and very high specificity. However, an unsolved challenge is that these proteins ultimately may become immunogenic in some patients, and provoke an immune response. The immunogenicity of the agents is dependent on specific properties, such as protein folding, aggregation, post-translational modifications and the presence of T and B cell epitopes. In clinical practice, a drug-evoked immune response can lead to a host of side effects, such as serum sickness, hypersensitivity, injection site reactions and hazardous cross-reactivity with endogenous proteins. More commonly, the immune response leads to a loss of drug efficacy because of the development of neutralizing or clearing anti-drug antibodies (ADAs).
Animal models may be useful in developing such low immunogenic drugs. On the one hand, animal models are used as predictive tools during drug development. On the other hand, animal models can help to elucidate the mechanisms underlying antibody responses against therapeutic proteins. Such knowledge is vital in developing novel therapeutic protein products with low immunogenicity.
Our Immunogenicity Animal Models
To overcome a classical immune response against “foreign” therapeutic proteins in conventional animal models, Creative Animodel has developed immune-tolerant transgenic mice that express the protein of interest. The mechanisms underlying antibody formation against the corresponding therapeutic protein are therefore expected to be similar to the mechanisms in humans. Our transgenic animal models can be used to predict neo-epitopes, relative immunogenicity and breaking of tolerance.
Immunogenicity Assay Validation Key PointsDetermination cut-offMinimum required dilution (MRD)Matrix effectDrug interferenceADA stabilityWithin- and between-series precision/accuracy
Creative Animodel has extensive experience and knowledge in developing in vivo immunogenicity in vitro immunotoxicity programs. Our immunogenicity assay experts utilize a multi-tiered approach to measure ADAs and neutralizing antibodies (NAbs), and are experienced in the development and validation of immunoassays. Through proactive communication and efficient management, we can help you to meet all immunogenicity testing requirements over your product’s development lifecycle. We will be pleasured to be your partner to make a contribution to human health. Look forward to working with you in the near future.