In our previous post, we outlined the dangers of Cytokine Release Syndrome (CRS) and the importance of preclinical Cytokine Release Assays (CRAs) when developing monoclonal antibodies (mAbs) that interact with the patient’s immune system. In this second post, we describe the different kinds of assays in use and how these may fit into your drug development program. An alternative type of CRA, peripheral blood mononuclear cell (PBMC) blood outgrowth endothelial cell (BOEC) co-culture, will be discussed in more detail in our next blog post.Continue reading
What is a cytokine storm?
Cytokine Release Syndrome (CRS), otherwise known as cytokine storm, is a systemic inflammatory response caused by complications due to disease, infection or an adverse effect of biologic therapy. The clinical symptoms of a cytokine storm are massive release of a potent cocktail of pro-inflammatory cytokines into the general circulatory system, leading to severe multi-organ damage, failure or potentially death. This is an extremely unwanted immunotoxicological side effect in drug development.Continue reading
The immune system is the body’s main defense against foreign materials and biologic agents such as bacteria, viruses, chemicals, and foreign cells and tissues. The immune response includes specific action of lymphocytes (one type of white blood cell) and is facilitated by other white blood cells, including neutrophils, monocytes, macrophages, eosinophils and basophils. The immune system can be viewed as a system controlled by negative feedback, meaning that normally it must reduce the effects of disturbance or invaders through self-regulation. Continue reading
Natural killer (NK) cells first earned their title as “killers” nearly 40 years ago when researchers observed the rapid immune response of these lymphocytes as they destroyed host cells infected with a virus or tumor cells. It seemed that NK cells could attach spontaneously without prior activation. Over time, researchers have learned more about the molecular mechanisms that regulate their activation and function.
Today, the NK cell assay is used to support specialty immunotoxicology studies for safety assessment. At Covance, we work with clients that often ask us about performing a NK cell functional analysis and the role of standard immunophenotyping to enumerate cells. This article addresses these questions by providing a brief background on the innate immunity of NK cell biology and comparing assay methods. Continue reading