Chemically linked Fab

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File:Chemically linked Fab'.svg
Example of chemically linked Fabs: two Fab' fragments 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.[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

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