FDA Develops Tool to Simulate Immune Response to Biologics
Researchers at the US Food and Drug Administration (FDA) have developed a new computational tool to predict whether the body will mount an immune response that blocks the activity of biological drugs.Specifically, the tool, dubbed TCPro, simulates how the body's CD4+ T cells will respond to biotherapeutics, and predicts whether the body will produce anti-drug antibodies.
"TCPro can be used to assess the potential for antibody formation even before the laboratory testing on biotherapeutics that is routinely done to screen for this risk," FDA writes, noting that traditional immunogenicity tests "can be expensive and time consuming."
This is due to the fact that major histocompatibility (MHC) class II molecules, which are found on the surface of antigen presenting cells (APCs) "are the most diverse in the human genome," making it challenging to collect cell samples that "accurately reflect the presence of all possible MHC-II proteins in a patient population."
For the TCPro test, the FDA researchers focused on identifying genes that would signify specific MHC-II expression to predict whether their immune systems would trigger a response to specific biotherapeutic proteins.
"Using TCPro, we can test virtual pools of subjects based on [major histocompatibility complex class II] (MHCII) frequencies and estimate immunogenicity risks for different populations," the researchers wrote in a paper published in American Association of Pharmaceutical Scientists' journal last month.
FDA says its researchers validated the test by comparing its predictions for 15 protein therapies against reported clinical data for those same products.
FDA