Chemically linked Fab
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.[1][2] 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.[3]
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,[3][4] but the concept was dropped because of high production costs.[5]
Bi-specific T-cell engagers employ a similar mechanism of action while being cheaper.
References[edit | edit source]
- ↑ , Production of target-specific effector cells using hetero-cross-linked aggregates containing anti-target cell and anti-Fc gamma receptor antibodies, The Journal of Experimental Medicine, 1984, Vol. 160(Issue: 6), pp. 1686–1701, DOI: 10.1084/jem.160.6.1686, PMID: 6239899, PMC: 2187539,
- ↑ , Preparation and performance of bispecific F(ab' gamma)2 antibody containing thioether-linked Fab' gamma fragments, Journal of Immunology, 1987, Vol. 139(Issue: 7), pp. 2367–2375, PMID: 2958547,
- ↑ 3.0 3.1 , Phase 1 trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin lymphoma, Blood, 2002, Vol. 100(Issue: 9), pp. 3101–3107, DOI: 10.1182/blood-2001-12-0295, PMID: 12384405,
- ↑ , 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, International Journal of Cancer, 1998, Vol. 77(Issue: 2), pp. 251–256, DOI: <251::AID-IJC14>3.0.CO;2-E 10.1002/(SICI)1097-0215(19980717)77:2<251::AID-IJC14>3.0.CO;2-E,
- ↑ Entwicklung und Charakterisierung bispezifischer Antikörper-Derivate zur Immuntherapie CD19-positiver Leukämien und Lymphome Full text, , Friedrich-Alexander-Universität, Erlangen-Nürnberg,
Engineered monoclonal antibodies and antibody mimetics | ||
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| Whole antibody |  | |
| Fab fragment | ||
| Variable fragment | ||
| Smaller units | ||
| Intracellular | ||
| Antibody mimetics | ||
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