Fab fragment

Structural model of a Fab fragment (ribbon model).

The Fab fragment , also called Fab antibody (from English fragment antigen binding ), is the antigen- binding fragment of an antibody that can be obtained by cleavage with the enzyme papain . A Fab fragment is a two amino acid chains structured protein , wherein each of the two chains, which are also referred to as light and heavy chain, each consisting of one variable and one constant antibody domain consists. Fab fragments are used as diagnostics and therapeutics in medicine . In addition, they are used as important tools in research and development.

properties

In contrast to classical antibodies such as immunoglobulin G (IgG), the Fab fragments lack the Fc units . Therefore, Fab fragments also lack the ability to directly trigger cytotoxic reactions by activating the complement system . Since the molecular mass of Fab fragments is usually below the kidney threshold and, due to the lack of the Fc unit, there are no active retention mechanisms, Fab have only a short plasma half-life . However, this can be extended by modification with polyethylene glycol ( PEGylation ).

Thanks to the fact that the molecular mass is about three times lower, Fab fragments have an improved ability to penetrate the tissue.

Manufacturing

The classic production of Fab fragments takes place from monoclonal or polyclonal antibodies with the help of enzymatic cleavage by papain. An effective way of producing Fab fragments is expression in cell cultures such as e.g. B. CHO cells .

Examples

Fab fragments are used as antidotes in particular in emergency medicine . These include the polyclonal and monoclonal digitalis antidotes directed against the cardiac glycosides digoxin and digitoxin . The developed Fab fragments directed against colchicine and against tricyclic antidepressants have been clinically tested, but are not commercially available. A polyclonal Fab fragment directed against rattlesnake venom, CroFab, has been approved in the United States for the treatment of rattlesnake bites since 2000.

With the increase in the share of biologicals on the pharmaceutical market, Fab fragments could also establish themselves in therapy. Abciximab was one of the first monoclonal Fab antibodies to be used therapeutically . This Fab fragment is directed against the glycoprotein GPIIb / IIIa on platelets and is used in the prophylaxis of vascular occlusion after percutaneous transluminal coronary angioplasty . Ranibizumab is a humanized, recombinant monoclonal anti- VEGF- A Fab fragment approved for the treatment of wet age-related macular degeneration . Certolizumab is a Fab fragment of a recombinant , humanized monoclonal antibody that has been conjugated to polyethylene glycol. The drug acts as a TNF blocker and is used to treat inflammatory bowel disease, Crohn's disease .

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

Individual evidence

↑ ^a ^b Hudson PJ, Souriau C: Engineered antibodies . In: Nat. Med. . 9, No. 1, January 2003, pp. 129-134. doi : 10.1038 / nm0103-129 . PMID 12514726 .
↑ Flanagan RJ, Jones AL: Fab antibody fragments: some applications in clinical toxicology . In: Drug Saf . 27, No. 14, 2004, pp. 1115-1133. PMID 15554746 .
↑ Seger D, Kahn S, Krenzelok EP: Treatment of US crotalidae bites: comparisons of serum and globulin-based polyvalent and antigen-binding fragment antivenins . In: Toxicol Rev . 24, No. 4, 2005, pp. 217-227. PMID 16499404 .
↑ Specialist information Lucentis ^® . Novartis Pharma. As of November 15, 2007.
↑ WJ Köstler, CC Zielinski: Diagnostic and therapeutic antibodies in oncology - State of the Art . In: Acta Chirurgica Austriaca . 32, No. 6, November 2000, pp. 260-263.

[pmid12514726-1] Hudson PJ, Souriau C: Engineered antibodies . In: Nat. Med. . 9, No. 1, January 2003, pp. 129-134. doi : 10.1038 / nm0103-129 . PMID 12514726 .

[pmid15554746-2] Flanagan RJ, Jones AL: Fab antibody fragments: some applications in clinical toxicology . In: Drug Saf . 27, No. 14, 2004, pp. 1115-1133. PMID 15554746 .

[pmid16499404-3] Seger D, Kahn S, Krenzelok EP: Treatment of US crotalidae bites: comparisons of serum and globulin-based polyvalent and antigen-binding fragment antivenins . In: Toxicol Rev . 24, No. 4, 2005, pp. 217-227. PMID 16499404 .

[4] Specialist information Lucentis ^® . Novartis Pharma. As of November 15, 2007.

[5] WJ Köstler, CC Zielinski: Diagnostic and therapeutic antibodies in oncology - State of the Art . In: Acta Chirurgica Austriaca . 32, No. 6, November 2000, pp. 260-263.