Chemically linked Fab explained

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,^[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.

Notes and References

1. 10.1084/jem.160.6.1686 . Karpovsky . B. . Titus . J. A. . Stephany . D. A. . Segal . D. M. . 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 . 160 . 6 . 1686–1701 . 1984 . 6239899 . 2187539.
2. 2958547 . 1987 . Glennie . M. J. . McBride . H. M. . Worth . A. T. . Stevenson . G. T. . Preparation and performance of bispecific F(ab' gamma)2 antibody containing thioether-linked Fab' gamma fragments . 139 . 7 . 2367–2375 . Journal of Immunology. 10.4049/jimmunol.139.7.2367 .
3. 10.1182/blood-2001-12-0295 . Phase 1 trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin lymphoma . 2002 . A. . Borchmann . Engert . P. . Blood . 100 . V. . 3101–3107 . Schnell . R. . Fuss . I. . Manzke . Diehl . O. . Davis . T. . Lewis . L. D. . Behnke . D. . Wickenhauser . C. . Schiller . P. . 12384405 . 9. free .
4. 10.1002/(SICI)1097-0215(19980717)77:2<251::AID-IJC14>3.0.CO;2-E . 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 . 1998 . Link . B. K. . Kostelny . S. A. . Cole . M. S. . Fusselman . W. P. . Tso . J. Y. . Weiner . G. J. . International Journal of Cancer . 77 . 2 . 251–256. 9650561 . free .
5. C. Kellner. Entwicklung und Charakterisierung bispezifischer Antikörper-Derivate zur Immuntherapie CD19-positiver Leukämien und Lymphome. Development and characterisation of bispecific antibody derivatives for the immunotherapy of CD19-positive leukaemia and lymphoma. German, English. Friedrich-Alexander-Universität. Erlangen-Nürnberg. 2008.