Complement system plays an essential role in host defense. As a first-class leader in drug discovery, Creative Biolabs has applied advanced therapeutic antibodies development based on numerous complement components. Combining our advanced technologies and long-term scientific expertise, we can offer high-quality and custom services to meet our clients’ demands precisely. Now we have successfully developed a series of innovative and effective therapeutic antibodies for complement-associated diseases.
Introduction of CD55 (DAF)
CD55, also known as decay-accelerating factor (DAF), is a 70 kDa glycosylphosphatidylinositol (GPI)-anchored membrane protein that inhibits both the classical and the alternative pathways of complement activation. It is widely expressed on the surface of all blood cells, vascular endothelial cells and various other tissue cells, acting as membrane-bound complement inhibitor to protect host cells from the destructive action of autologous complement. Now, it has become an important target for therapeutic antibody exploration.
Structure of CD55 (DAF)
The structure of DAF is characterized by four complement control protein repeats (CCP1, CCP2, CCP3, and CCP4) with a single N-linked glycosylation site between CCP1 and CCP2, a heavily O-glycosylated membrane proximal domain rich in serine, threonine and proline and a glycosylphosphatidylinositol (GPI) anchor. Among which, CCP 2-4 and three consecutive lysine residues in a positively charged pocket between CCP2 and CCP3 are involved in its inhibition of the alternative complement pathway. While CCP2 and CCP3 alone are involved in its inhibition of the classical pathway.
Fig.1 The Structure of the CD55 protein.
Functions and Clinical Significance of CD55 (DAF)
Fig.2 Intravascular and extravascular hemolysis in PNH. (Hill, et al., 2017)
Because of the importance of regulating both the classical and the alternative pathways of complement activation, DAF has become a promising and effective target for therapeutic antibody exploration and clinical trial. Creative Biolabs can offer a full range of formulation development services for complement drug products.
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References
A: Identifying drug candidates for CD55 typically involves a multi-step process. Initially, researchers perform extensive biological assays and screenings to identify molecules or compounds that interact with CD55 and modulate its activity. High-throughput screening, virtual screening, and molecular modeling techniques are often used in this phase. Once potential candidates are identified, they undergo rigorous in vitro and in vivo testing to assess their safety and efficacy.
A: One challenge is the potential for immunosuppression when modulating the complement system, as it has both protective and destructive roles in the immune response. Striking a balance between therapeutic benefit and safety is crucial. Additionally, drug delivery to specific tissues or cells where CD55 is involved may be challenging, depending on the disease being targeted.
A: Extensive preclinical studies are conducted. These studies include in vitro experiments using cell cultures and in vivo experiments in animal models to evaluate the safety, pharmacokinetics, and efficacy of the drug candidate. Researchers also study the drug's potential side effects and its impact on CD55-related pathways.