Immunogenicity Assessment

New technique, in combination with the use of artificial intelligence, allows fragments of antibodies to be screened for susceptibility to aggregation caused by structure disruption much earlier in the drug discovery process. Protein/Antibody therapies can be highly effective in treating disease. The failure rate of protein candidates upon manufacturing at industrial scale is a significant problem, emerging in the late stage of development process. With the protein/antibody sequence information gathered into our database and getting bigger, the screening system is underdeveloped using AI methods. CD ComputaBio's AI platform has a range of proteins to screen and to determine which are more likely to progress through the development process.

Immunogenicity Testing

FDA has announcing the availability of a final guidance for industry entitled “Immunogenicity Testing of Therapeutic Protein Products—Developing and Validating Assays for Anti-Drug Antibody Detection.” Immunogenicity is the intrinsic capacity of a product to induce an immune response in a target population. Immunogenicity testing assays provide a way to measure the potential immune responses of biologics and biosimilars.

Immunogenicity is important for both vaccines and therapeutic proteins.

Designed to raise an immune response to provide protection in fighting a disease.
Designed to exert a specific therapeutic function (biological activity) ------ Efficacy / Activity
Anti-drug antibody (ADA) response to protein drugs may reduce efficacy, compromise the pharmacodynamics and safety, and lead to severe side effects in some cases. ------Toxicity / Safety

Figure 1 Potential Causes of Immunogenicity

In Vitro Bioassays

Based on clinical samples (human PBMC bank)
Innate immune response

Whole PBMC/DC activation – impact of proteins and impurities
Adaptive immune response

MAPPs (MHC-Associated Peptide Proteomics)
T cell activation assays (native and memory)
Immunotoxicology

Impact of mode of action
Off-target binding

In silico Services Profile

HLA Class I (CD8+) and HLA Class II (CD4+)
Global or Caucasian population
TCR Filters

In silico T Cell Epitope Prediction

Advantages

Antibody discovery and screening expertise
Leading knowledge of protein structure and aggregation
AI-Assisted Antibody Selection platform

Experts from CD ComputaBio are dedicated to helping researchers and pharmaceutical companies to identify patterns in protein sequences, and inform our clients whether a drug can be scaled up for production.