Chemically linked Fab
Encyclopedia
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
. 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.
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, but the concept was dropped because of high production costs.
Bi-specific T-cell engagers employ a smilar mechanism of action while being cheaper.
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
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
Monoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
and are linked by chemical means like a thioether
Thioether
A thioether is a functional group in organosulfur chemistry with the connectivity C-S-C as shown on right. Like many other sulfur-containing compounds, volatile thioethers have foul odors. A thioether is similar to an ether except that it contains a sulfur atom in place of the oxygen...
. Typically, one of the Fabs binds to a tumour antigen (such as CD30
CD30
CD30, also known as TNFRSF8, is a cell membrane protein of the tumor necrosis factor receptor family and tumor marker.This receptor is expressed by activated, but not by resting, T and B cells. TRAF2 and TRAF5 can interact with this receptor, and mediate the signal transduction that leads to the...
) and the other to a protein on the surface of an immune cell, for example an Fc receptor
Fc receptor
An Fc receptor is a protein found on the surface of certain cells - including natural killer cells, macrophages, neutrophils, and mast cells - that contribute to the protective functions of the immune system....
on a macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
. In this way, tumour cells are attached to immune cells, which destroy them.
In the late 1990s and early 2000s, clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s with chemically linked Fabs were conducted for the treatment of various types of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. Early results were promising, but the concept was dropped because of high production costs.
Bi-specific T-cell engagers employ a smilar mechanism of action while being cheaper.