Immunological safety studies are vital to ensure patient safety throughout development release
Many of the immunomodulatory effects of mAbs are desirable and clinically efficious. However, activation or suppression/depletion of non-target immune cells and mediators, or permanent non-reversible changes to immune target cells/pathways, or any unintended sequelae of the intended pharmacology, e.g., cell and tissue injury, inflammation, 'cytokine storms,' tumor lysis syndrome, infection and cancer, autoimmunity, hypersensitivity, would be considered to be or reflect immunotoxicity. These often adverse consequences can result from exaggerated or prolonged activity of the mAb binding to the desired target antigen on the desired target cells/mediators, modulating a target with pleiotropic immune functions, including those whose modification is not required for therapeutic benefit, or modulating a target that is also expressed on non-immune cells or other immune cells besides those that are the intended therapeutic focus. Some of these immunological safety concerns can be reduced or circumvented by rational mAb design, e.g., through the use of an 'inert' IgG isotype with little or no effector function, or by screening mAb candidates for reduced cytokine release, DC activation and immunogenicity potential.