If you want to protect yourself from an infection, you get a vaccination, e.g. non infectious viral proteins. Your immune system reacts with several mechanism and also produces antibodies to attack foreign proteins.
The same can happen, if you get multiple doses of biopharmaceuticals (BP) such as monoclonal antibodies conjugated with specific drugs. The immune system might generate an unwanted immune response. The ADA (anti-drug-antibodies) can potentially decrease the efficacy of the drug, modify the clearance or induce hypersensitive reactions. Due to the safety issues associated with immunogenicity, it is of great importance to reduce the risk for immunogenicity in the clinic.
The scientist from Novo Nordisk A/S published a novel approach in PLOS ONE about the developend a new assay for early drug testing during the development. This novel assay uses CD4+-enriched T cells and irradiated PBMCs comprising the APC population, and the effects of the biopharmaceuticals are tested by cell prolifation and cytokine secretion (IL-2 Elispot).
Advantages to other immune cell assays:
- Controlled number of specific T cells
- Stronger response of enriched specific T cell fraction
- no generation of DCs needed - hence allowing high througput analysis, cytokine contribution from non-specific cells can be limited
- 2 independent read outs of the immune response and activation
The results they present in “Quantitative analysis of the CD4+ T cell response to therapeutic antibodies in healthy donors using a novel T cell:PBMC assay”, show that the novel test can evaluate the immunogenicity potential of biopharmaceuticals in a very early stage of drug development. They also show that in vitro immunogenicity tests of several known BPs are also documented in clinical trials.
The selection of the right drug candidates with low immunogenicity potential is crucial to increase the patients safety.
Written by Peter
Scientific Support Specialist, Lonza Pharma-Bioscience Solutions at Lonza
