Chemically linked Fab: Difference between revisions

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[[File:Chemically linked Fab'.svg|thumb|300px|Example of chemically linked Fabs: two [[Fab' fragment]]s linked with a thioether, resulting in a F(ab')<sub>2</sub>. The molecule is bound to a tumour cell via the tumour antigen [[CD30]] and to a [[macrophage]] via an [[Fc receptor]].]]
{{Short description|A type of antibody fragment used in medical and research applications}}
Two '''chemically linked fragments antigen-binding''' form an artificial [[antibody]] that binds to two different [[antigens]], making it a type of [[bispecific antibody]]. They are [[fragment antigen-binding|fragments antigen-binding]] (Fab or Fab') of two different [[monoclonal antibodies]] and are linked by chemical means like a [[thioether]].<ref>{{Cite journal
| doi = 10.1084/jem.160.6.1686
| last1 = Karpovsky | first1 = B.
| last2 = Titus | first2 = J. A.
| last3 = Stephany | first3 = D. A.
| last4 = Segal | first4 = D. M.
| title = Production of target-specific effector cells using hetero-cross-linked aggregates containing anti-target cell and anti-Fc gamma receptor antibodies
| journal = The Journal of Experimental Medicine
| volume = 160
| issue = 6
| pages = 1686–1701
| year = 1984
| pmid = 6239899
| pmc = 2187539
}}</ref><ref>{{Cite journal
| pmid = 2958547
| year = 1987
| last1 = Glennie | first1 = M. J.
| last2 = McBride | first2 = H. M.
| last3 = Worth | first3 = A. T.
| last4 = Stevenson | first4 = G. T.
| title = Preparation and performance of bispecific F(ab' gamma)2 antibody containing thioether-linked Fab' gamma fragments
| volume = 139
| issue = 7
| pages = 2367–2375
| journal = Journal of Immunology
}}</ref> Typically, one of the Fabs binds to a [[tumour antigen]] (such as [[CD30]]) and the other to a protein on the surface of an [[immune cell]], for example an [[Fc receptor]] on a [[macrophage]]. In this way, tumour cells are attached to immune cells, which destroy them.<ref name="Borchmann">{{Cite journal
| doi = 10.1182/blood-2001-12-0295
| title = Phase 1 trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin lymphoma
| year = 2002 | first11 = A.
| last1 = Borchmann
| last11 = Engert | first1 = P.
| journal = Blood
| volume = 100 | first10 = V.
| pages = 3101–3107
| last2 = Schnell | first2 = R.
| last3 = Fuss | first3 = I.
| last4 = Manzke
| last10 = Diehl | first4 = O.
| last5 = Davis | first5 = T.
| last6 = Lewis | first6 = L. D.
| last7 = Behnke | first7 = D.
| last8 = Wickenhauser | first8 = C.
| last9 = Schiller | first9 = P.
| pmid = 12384405
| issue = 9
}}</ref>


In the late 1990s and early 2000s, [[clinical trial]]s with chemically linked Fabs were conducted for the treatment of various types of [[cancer]]. Early results were promising,<ref name="Borchmann" /><ref>{{Cite journal
== Chemically Linked Fab ==
| doi = 10.1002/(SICI)1097-0215(19980717)77:2<251::AID-IJC14>3.0.CO;2-E
| title = Anti-CD3-based bispecific antibody designed for therapy of human B-cell malignancy can induce T-cell activation by antigen-dependent and antigen-independent mechanisms
| year = 1998
| last1 = Link | first1 = B. K.
| last2 = Kostelny | first2 = S. A.
| last3 = Cole | first3 = M. S.
| last4 = Fusselman | first4 = W. P.
| last5 = Tso | first5 = J. Y.
| last6 = Weiner | first6 = G. J.
| journal = International Journal of Cancer
| volume = 77
| issue = 2
| pages = 251–256
}}</ref> but the concept was dropped because of high production costs.<ref>{{cite web|first1=C|last1=Kellner|url=http://www.opus.ub.uni-erlangen.de/opus/volltexte/2009/1235/|title=Entwicklung und Charakterisierung bispezifischer Antikörper-Derivate zur Immuntherapie CD19-positiver Leukämien und Lymphome|trans-title=Development and characterisation of bispecific antibody derivatives for the immunotherapy of CD19-positive leukaemia and lymphoma|language=German, English|publisher=Friedrich-Alexander-Universität|location=Erlangen-Nürnberg|year=2008}}</ref>


[[Bi-specific T-cell engager]]s employ a similar mechanism of action while being cheaper.
'''Chemically linked Fab''' refers to a type of [[antibody fragment]] that is engineered by chemically linking two [[Fab fragments]]. Fab fragments are the antigen-binding regions of an [[antibody]], consisting of one constant and one variable domain from each of the heavy and light chains of the antibody. These fragments retain the ability to bind to specific [[antigens]], making them useful in various [[biomedical]] and [[therapeutic]] applications.


==References==
== Structure and Function ==
{{reflist}}


{{Engineered antibodies}}
The Fab fragment is derived from the [[immunoglobulin]] molecule by enzymatic digestion, typically using the enzyme [[papain]]. This process cleaves the antibody into two Fab fragments and one [[Fc fragment]]. Each Fab fragment contains a complete antigen-binding site, which includes the [[variable region]]s of both the heavy and light chains.


[[Category:Monoclonal antibodies]]
In chemically linked Fab, two Fab fragments are covalently linked to enhance their stability and binding affinity. This linkage can be achieved through various chemical methods, such as using [[cross-linking agents]] that form stable bonds between the fragments. The resulting dimeric structure can improve the pharmacokinetic properties of the Fab, such as increased serum half-life and enhanced tissue penetration.
[[Category:Antineoplastic drugs]]


== Applications ==


{{monoclonal-antibody-stub}}
Chemically linked Fab fragments are utilized in several [[clinical]] and [[research]] settings:
{{antineoplastic-drug-stub}}
 
{{dictionary-stub1}}
* '''Therapeutics''': They are used in the development of [[biopharmaceuticals]] for the treatment of diseases, including [[cancer]] and [[autoimmune disorders]]. Their smaller size compared to full antibodies allows for better tissue penetration and reduced immunogenicity.
 
* '''Diagnostics''': In [[diagnostic assays]], chemically linked Fab fragments can be used to detect specific antigens with high sensitivity and specificity. They are often employed in [[immunoassays]] and [[biosensors]].
 
* '''Research''': In [[biomedical research]], these fragments are used to study [[antigen-antibody interactions]] and to map [[epitopes]] on antigens. Their ability to bind specific targets makes them valuable tools in [[molecular biology]] and [[biochemistry]].
 
== Advantages ==
 
Chemically linked Fab fragments offer several advantages over full-length antibodies:
 
* '''Reduced Size''': Their smaller size allows for better tissue penetration and access to epitopes that may be sterically hindered for full antibodies.
 
* '''Lower Immunogenicity''': The absence of the Fc region reduces the potential for immune system activation, making them safer for therapeutic use.
 
* '''Enhanced Stability''': Chemical linkage can improve the stability of Fab fragments, making them more suitable for therapeutic and diagnostic applications.
 
== Limitations ==
 
Despite their advantages, chemically linked Fab fragments also have some limitations:
 
* '''Production Complexity''': The chemical linking process can be complex and may require optimization to achieve the desired stability and activity.
 
* '''Shorter Half-life''': Compared to full antibodies, Fab fragments generally have a shorter serum half-life, which may necessitate more frequent dosing in therapeutic applications.
 
== Related Pages ==
 
* [[Antibody]]
* [[Fab fragment]]
* [[Immunoglobulin]]
* [[Antigen]]
* [[Biopharmaceutical]]
 
[[Category:Antibody fragments]]
[[Category:Biotechnology]]
[[Category:Immunology]]

Latest revision as of 19:24, 22 March 2025

A type of antibody fragment used in medical and research applications


Chemically Linked Fab[edit]

Chemically linked Fab refers to a type of antibody fragment that is engineered by chemically linking two Fab fragments. Fab fragments are the antigen-binding regions of an antibody, consisting of one constant and one variable domain from each of the heavy and light chains of the antibody. These fragments retain the ability to bind to specific antigens, making them useful in various biomedical and therapeutic applications.

Structure and Function[edit]

The Fab fragment is derived from the immunoglobulin molecule by enzymatic digestion, typically using the enzyme papain. This process cleaves the antibody into two Fab fragments and one Fc fragment. Each Fab fragment contains a complete antigen-binding site, which includes the variable regions of both the heavy and light chains.

In chemically linked Fab, two Fab fragments are covalently linked to enhance their stability and binding affinity. This linkage can be achieved through various chemical methods, such as using cross-linking agents that form stable bonds between the fragments. The resulting dimeric structure can improve the pharmacokinetic properties of the Fab, such as increased serum half-life and enhanced tissue penetration.

Applications[edit]

Chemically linked Fab fragments are utilized in several clinical and research settings:

  • Therapeutics: They are used in the development of biopharmaceuticals for the treatment of diseases, including cancer and autoimmune disorders. Their smaller size compared to full antibodies allows for better tissue penetration and reduced immunogenicity.
  • Diagnostics: In diagnostic assays, chemically linked Fab fragments can be used to detect specific antigens with high sensitivity and specificity. They are often employed in immunoassays and biosensors.

Advantages[edit]

Chemically linked Fab fragments offer several advantages over full-length antibodies:

  • Reduced Size: Their smaller size allows for better tissue penetration and access to epitopes that may be sterically hindered for full antibodies.
  • Lower Immunogenicity: The absence of the Fc region reduces the potential for immune system activation, making them safer for therapeutic use.
  • Enhanced Stability: Chemical linkage can improve the stability of Fab fragments, making them more suitable for therapeutic and diagnostic applications.

Limitations[edit]

Despite their advantages, chemically linked Fab fragments also have some limitations:

  • Production Complexity: The chemical linking process can be complex and may require optimization to achieve the desired stability and activity.
  • Shorter Half-life: Compared to full antibodies, Fab fragments generally have a shorter serum half-life, which may necessitate more frequent dosing in therapeutic applications.

Related Pages[edit]

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