Complement System
Taligen Therapeutics’ technologies focus on controlling the amplification of complement activation through inhibition of factor B and by delivering endogenous inhibitors of complement amplification specifically to sites where complement activation is occurring.
Publications related to Taligen Technology
- Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection
- Complement receptor 2–mediated targeting of complement inhibitors to sites of complement activation
- Factor B of the alternative complement pathway regulates development of airway hyperresponsiveness and inflammation
- The Central Role of theAlternative Complement Pathway in Human Disease
- A novel inhibitor of the alternative complement pathway prevents antiphospholipid antibody-induced pregnancy loss in mice
The complement system consists of a group of functionally inter-related proteins which are key components of the innate immune system. Activation of the complement pathway is one of the major means by which the body recognizes foreign antigens, pathogens and allergens as well as tissue injury, ischemia, apoptosis and necrosis. Activation of complement occupies a critical position proximal in the inflammatory cascade, leading to the generation of multiple downstream pro-inflammatory events, including chemotaxis of inflammatory cells and release of cytokines and enzymes which directly mediate tissue damage. Thus, control of complement activation is capable of inhibiting the expression of multiple pro-inflammatory mediators.
Complement Cascade
Complement can be activated by one of three pathways: the classical, lectin or alternative pathway (see figure). Activation of complement by any of the three pathways leads to cleavage of the major serum complement component (C3) and initiation of a cascade of activation in which a number of pro-inflammatory molecules are released including C3a, C5a, and the membrane attack complex (MAC). In this process, C3b becomes covalently bound to nearby tissues and thereby serves as a ligand for complement receptors (CR) which are present on a variety of immune cells. The CR-mediated binding of these cells to tissue-bound C3b further contributes to the generation of the inflammatory response.
Of the three pathways of complement activation, the alternative pathway is unique in that it acts as a potent amplification mechanism for the complement system. Driven by the presence of small amounts of activated C3, the alternative pathway is capable of amplifying the generation of pro-inflammatory complement activation products by 50-100 fold. This amplification of complement activation has been shown to be critical in driving inflammatory disease processes.
Taligen’s technologies focus on controlling the amplification of complement activation: a monoclonal antibody which targets factor B (TA106) is designed to inhibit the activation of the alternative pathway of complement, and the Targeted Inhibitor Program (TT30) allows for delivering endogenous inhibitors of the alternative pathway specifically to sites where complement activation is occurring.