Complement-Dependent Cytotoxicity

After summarizing how the complement system can have both anti-tumor and pro-tumor effects, we conclude our blog series on Reis et al. by discussing the clinical aspects of complement as a target and biomarker.  As discussed in the previous blogs, the imbalance in activation of complement leads to overproduction of complement proteins that causes a switch from immunosurveillance to tumorigenesis.  Thus, therapeutics may be developed that target complement proteins and fragments to restore balance and an effective immune environment. Using complement to enhance monoclonal antibody-based (mAb) therapies Engineering antibodies to enhance Fc region-mediated effector functions have been well [...]

Complement in promotion of tumorigenesis. The imbalance and dysfunction of complement activity and activation can lead to various mechanisms that promote tumorigenesis. These mechanisms can have affects on the immune cells to provide a more favorable tumor growth environment, including: 1) recruitment of MDSCs, 2) suppression of effector T cell function, and 3) sustained release of pro-inflammatory factors for favorable tumor growth. In addition, loss of complement regulation has affects on non-immune cells that sustain tumor growth and metastasis, including: 1) angiogenesis, 2) abnormal tumor cell proliferation, and 3) cell invasion and metastasis. Please see our blogs for more [...]

The complement system of the innate immune system has been widely regarded as an early deterrent to infections and a means to clear pathogens by activating a group of proteins that leads to cell lysis, phagocytosis, and inflammation.  In addition, the power of complement has been implicated as a mechanism by which therapeutic antibodies, such as Rituxan, promoted their anti-tumor effects.  Along those lines, many biotechnology and pharmaceutical companies have tried to harness that power in targeted monoclonal antibody (mAb) cancer therapies.  However, more recent findings have indicated that, like everything about the immune system, balance is key and dysregulation [...]

What is CDC and why would you need it? This is Part 2 of our series, “The Power of Complements…”. Miss Part 1? Catch up here. Potential applications & implications for CDC assays As alluded to in Part 1, one of the most important applications for CDC assays is to determine if a potential therapeutic antibody can mediate CDC activity. Originally thought to only prevent downstream signaling of the target receptor by blocking its oligomerization or engagement to ligands, most therapeutic antibodies are now suggested to work through multiple mechanisms, including CDC activity. Thus, many companies screen their therapeutic antibody [...]

What is CDC and why would you need it? What is Complement-Dependent Cytotoxicity? Complement-Dependent Cytotoxicity (CDC) is a form of cytotoxicity mediated by the host organism’s complement system. Components of the complement system become activated by three main mechanisms and all pathways lead to the formation of the membrane attack complex (MAC) on a target cell or organism. This MAC creates an opening in the plasma membrane of the cell or organism to drive death by osmotic lysis. What is the complement system and what are its associated pathways? A host organism’s complement system consists of over 30 proteins, including [...]