Kerstin Pohl, sr. global manager, Gene Therapies, at SCIEX, and Thomas Kofoed, co-founder of Alphalyse, discussed the harmful effects of HCPs and strategies to mitigate them.
Key Insights:
- Host cell proteins (HCPs) may disrupt drug functionality and pose the risk of severe levels of undesired immunogenicity. They must be thoroughly assessed and eliminated during manufacturing.
- Immunoassays frequently only estimate the overall HCP quantity and cannot provide information about individual HCPs, and they tend to neglect weak immunogens.
- Liquid chromatography-mass spectrometry (LC-MS) offers robust, sensitive and unbiased profiling of HCPs and can be leveraged to minimise process-related impurities.
Genomic medicine and gene-based vaccines show immense promise for treating cancer and rare diseases, correcting for gene deficiencies and accelerating vaccine production. However, purification of these products can be quite intricate, and incomplete purification can lead to complications. Most recently, one of the FDA-approved adenoviral COVID-19 vaccines was associated with vaccine-induced thrombosis with thrombocytopenia syndrome (VITT) with 1:125,000 frequency, inducing blood clotting in vital organs. Although the factors leading to VITT are still being studied, investigation of the vaccine components revealed adenoviral proteins that may have stimulated antibody production for attacking platelet factor 4 (PF4), triggering coagulation.