Fragment antigen-binding

The Fab fragment also Fab antibody ( ENGL. Fragment antigen binding), the antigen-binding fragment of an antibody that can be obtained by digestion with the enzyme papain. A Fab fragment is a built up of two amino acid chains, proteins, each of the two chains, which are also referred to as light and heavy chain, each consisting of one variable and one antibody constant domain. Fab fragments are used as diagnostic and therapeutic agents in medicine. In addition, they are used as important tools in the research and development.

Properties

In contrast to classical antibodies, such as immunoglobulin G ( IgG), missing the Fab fragments of the Fc units. Therefore, Fab fragments lack the ability to directly induce cytotoxic reactions by activation of the complement system. Since the molecular weight of Fab fragments is generally below the renal threshold, and due to the absence of the Fc moiety no active retaining mechanisms exist, Fab have a short plasma half-life. This can, however, by modification with polyethylene glycol extend ( PEGylation ).

Thanks to the lower by about a factor of three molecular mass, Fab fragments have an improved ability to penetrate into the tissue.

Production

The classical preparation of Fab fragments of monoclonal or polyclonal antibodies is performed using the enzymatic cleavage by papain. An effective way of production of Fab fragments is expressed in cell cultures such as CHO cells.

Examples

Fab fragments are used in particular in emergency medicine as an antidote application. These include directed against the cardiac glycosides digoxin and digitoxin polyclonal and monoclonal Digitalis Antidote. The Fab fragments developed, directed against colchicine and against tricyclic antidepressants were indeed clinically tested, but are not commercially available. A directed against the Rattlesnake venom polyclonal Fab fragment CroFab is approved since 2000 in the U.S. to treat rattlesnake bites.

With the increase in the proportion of biologicals in the pharmaceutical market, also Fab fragments were able to establish in therapy. One of the first monoclonal Fab antibody was used therapeutically is abciximab. This Fab fragment directed against the platelet glycoprotein on GPIIb / IIIa, and is used in the prophylaxis of vascular occlusion after percutaneous transluminal coronary angioplasty. Ranibizumab is a humanized recombinant monoclonal, directed against VEGF -A Fab fragment, which is approved for the treatment of wet age -related macular degeneration. Certolizumab is a Fab fragment of a recombinant humanized monoclonal antibody, which was conjugated to polyethylene glycol. The drug acts as an anti-TNF, and used in the treatment of inflammatory bowel disease Crohn's disease.

Also in the diagnosis Fab fragments bet. Arcitumomab, is a Fab fragment of a murine monoclonal antibody that recognizes an epitope of the carcinoembryonic antigen ( CEA). This protein is synthesized particularly strong in the embryonic intestinal mucosa and in carcinomas of the gastrointestinal tract. CEA is suitable as a recognition molecule for presentation of metastatic carcinomas. Sulesomab is also a Fab fragment of a murine monoclonal antibody which recognizes an epitope on the surface of granulocytes. It can be used to infection and inflammation, for example in patients with osteomyelitis, represent.