Chemically linked Fab
File:Chemically linked Fab'.svgs linked with a thioether, resulting in a F(ab')2. The molecule is bound to a tumour cell via the tumour antigen CD30 and to a macrophage via an Fc receptor.]]
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 fragments antigen-binding (Fab or Fab') of two different monoclonal antibodies and are linked by chemical means like a thioether.{{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
| 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
| doi = 10.4049/jimmunol.139.7.2367
}} 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.{{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
| doi-access = free
}}
In the late 1990s and early 2000s, clinical trials with chemically linked Fabs were conducted for the treatment of various types of cancer. Early results were promising,{{Cite journal
| 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
| pmid = 9650561
| doi-access = free
}} but the concept was dropped because of high production costs.{{cite thesis|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}}
Bi-specific T-cell engagers employ a similar mechanism of action while being cheaper.
References
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{{Engineered antibodies}}
Category:Monoclonal antibodies
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