Evaluation of the Immunogenicity of Therapeutic Protein Products - FDA Scientists developed a new Tool

Over the past two decades, the number of biological agents has steadily increased. Particularly in the case of biological drugs that affect  the disease mechanisms of immune diseases - such as certain rheumatic and dermal diseases and intestinal inflammations - the active substances are structurally immunogenic and trigger reactions in the patient's body. In most cases, these reactions are only of minor relevance and weak. Occasionally, however, these drugs trigger a complete cellular and humoral immune response and lead to hypersensitivity reactions or even to the total loss of treatment success. Therefore, the investigation of immunogenicity in therapeutic biological agents is of particular importance, especially in view of the production and availability of biosimilars, i.e. biological generics.

The New Tool

In this context, scientists from the U.S. Food and Drug Administration (FDA) have now developed a mathematical tool that uses simulation to predict the possible production of antibodies against biotherapeutic protein compounds. The mathematical tool TCPro evaluates the reaction of CD4+ T cells of the immune system to certain biotherapeutics. These cells induce or control the response of the immune system to biotherapeutics, including the production of antibodies by the B cells.

This possibility of calculation is already important in the early phase of drug development, where the potential for undesired immune reactions has to be determined, i.e. their immunogenicity risk. The FDA describes the benefits of the new tool as follows:

"TCPro can be used to estimate the potential for antibody formation prior to laboratory testing of biotherapeutics routinely used for risk assessment. Such tests, in which human T cells are grown in contact with the drug and then growth is measured, can be expensive and time-consuming. The FDA tool provides a fast and cost-effective way to test both new biotherapeutic proteins and new protein fragments added during biodevelopment of the drug."

In a study published in the AAPS Journal, "TCPro: An In Silico Risk Assessment Tool for Biotherapeutic Protein Immunogenicity", FDA scientists showed that the predictions about the immune response risk of 15 protein-based biotherapeutics were consistent with actual reported clinical experience.

The corresponding FDA announcement can be found on the FDA website under the title "TCPro simulates immune system response to biotherapeutic drugs".

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