Potent biological molecules, especially those with a novel mechanism of action, benefit from in vitro testing on human material prior to a clinical trial. Insights from such testing are invaluable, both for risk mitigation and for the management of symptoms in the clinic. Our platform can aid the screening process, determine the safety profile and establish the appropriate first dose in humans, contributing in many ways to the overall success of early clinical trials. EMA has issued guidelines to identify and mitigate risks in early clinical trials. Among the key elements is a requirement for preclinical safety evaluation using human blood to determine the potential cellular activation of biotherapeutics. You can access these guidelines here.
Therapeutic monoclonal and polyspecific antibodies, which are biological drugs developed to treat human diseases such as cancer and autoimmune diseases, comprise one of the most rapidly growing groups of advanced biopharmaceuticals. Polyspecific monoclonal antibodies are genetically engineered proteins that can simultaneously engage two or more different types of epitopes. Of these antibodies, the most commonly used are bispecific antibodies that contain two different antigen-binding sites in one molecule. Apart from their therapeutic effect, antibodies can cause unexpected side effects, including the activation of immune cells and the release of factors that collectively induce a severe systemic immune activation, such as cytokine release syndrome (CRS). Because of the potential for side effects like CRS, all biological drugs require safety testing before a clinical trial can take place.
The therapeutic effect of antibodies occurs through the binding of a target cell, which can have an antagonistic, agonistic, blocking or cell-depleting net effect. The killing of a target cell that a monoclonal antibody has bound to can take place through two major mechanisms: antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). Immuneed’s platform is unique in its ability to study these mechanisms simultaneously. By specifically blocking the different mechanisms in our assay, the responsible killing mechanism can be identified for antibodies that are known to induce target cell death.