Antibody Fab-fragment

Smith, T.W. Butler, W.P. Haber, E. Fozzard, H. Marcus, F.I. Bremner, W.F. Schulman, I.C. and Phillips, A. Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. N Fnal J Med 307(22) 1357-1362, 1982. 

Figure 21.11 Fab antibody fragments containing free thiols can be activated with Ellman s reagent to form a sulfhydryl-reactive derivative. A-chain toxin subunits containing a free thiol group may be coupled to the activated Fab molecule to produce an immunotoxin complex.

Flanagan RJ, Jones AL. Fab antibody fragments some Applications in clinical toxicology. Review article. Drug Saf2004 27(14) 1115-33. 

Production of Human Fab Antibody Fragments from Phage Display Libraries... 

For detection of Fab antibody fragments, use a polyclonal rabbit IgG to human k and X light chains and HRP-conjugated goat antirabbit IgG (see Note 9). 

A major source of human antibodies are phage display libraries, which are constructed from various genetic sources. Antibodies are expressed as scFV and Fab antibody fragments using various vector systems. This review offers a comprehensive overview of M13 phage display antibody vectors and discusses their applications. 

Merdan, T., Callahan, J., Petersen, H., Kunath, K., Bakowsky, U., Kopeckova, P., Kissel, T., and Kopecek, J. (2003) Pegylated polyethylenimine-Fab antibody fragment conjugates for targeted gene delivery to human ovarian carcinoma cells. 

Antman E, Wenger TL, Butler VP Jr, Haber E, Smith TW. Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments Final report of a multicenter study. Circulation 1990 81 1744-52. 

Human antichimeric antibodies, specific to the murine epitope of Fab antibody fragments, have been observed in patients treated with abciximab. These antibodies are IgG antibodies and have so far not correlated with any adverse effects (12). 

There have been reports of the use of exchange transfusion to remove Fab antibody fragment-digoxin complexes in patients with acute anuric renal insufficiency (194). 

Safadi R, Levy 1, Amitai Y, Caraco Y. Beneficial effect of digoxin-specific Fab antibody fragments in oleander intoxication. Arch Intern Med 1995 155(19) 2121-5. 

Figure 3-16 Model of bacteriophage fd engineered to display peptides as inserts in the coat proteins of the virus. The native virus structure is shown in gray proteins not present in the native virus are shown black or green, inserted near the N-termini of some major coat proteins is a 6-residue peptide. To one of these peptides a specific Fab antibody fragment (green) has bound from solution, and a second Fab is shown nearby. The N-terminal region of a minor coat protein at the end of the virion has been engineered to display a (different) Fab fragment. Steric constraints are less stringent for inserts in the minor proteins, but fewer copies per virion are possible. Reprinted with permission from Barbas, et...

Shumaik GM, Wu AW, and Ping AC (1988) Oleander poisoning treatment with digoxin-specific Fab antibody fragments. Annals of Emergency Medicine 17 732-735. 

Serious ingestions require cardiac monitoring in an intensive-care setting. Hypotension may be resistant to dopamine and dobutamine. Norepinephrine can also be used. Bradycardia can be treated with atropine and a temporary pacemaker as needed. Digoxin-specific FAB antibody fragments have been used with some success for cardiac conduction abnormalities after a yew exposure. If no contraindication, lido-caine, amiodarone, or procainamide may be used for ventricular dysrhythmias. 

Fig. 12 Microphotograph of an analyte concentrator fabricated with FAb antibody fragments immobilized to controlled-pore glass silica. The irregularly shaped beads were housed between two frit structures. The analyte concentrator device was connected to two separation capillaries by a Teflon sleeve. The plastic connector was glued to the separation capillaries by an epoxy resin. The entire fabrication process was monitored by an stereo microscope. (For details of experimental conditions, see Ref. 120.)...

Pharmacodynamics. Since ranibizumab is delivered via an intravitreal injection, studies were undertaken to determine if the drug could cross the neural retina and access the subretinal space where the CNV lesions are located. A study in rhesus monkeys demonstrated that 25 pg in 50 pL of Fab antibody fragment diffused through the neural retina to the retinal pigment epithelial layer after one hour and persisted in this location for up to seven days (10). The half-life in the vitreous was 3.2 days. These data are consistent with the results of a pharmacokinetic study done by a noninvasive fluorophotometric method that showed that fluorescein-labeled ranibizumab disappeared from the vitreous with a mean terminal half-life of 2.9 days and a mean residence time of 4.2 days (11). 

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