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7.2.6 Anti-idiotype antibodies

The binding site of an anti-idiotype antibody is a copy of an epitope. They are made by

deriving a primary monoclonal antibody to the epitope of interest, usually a cell

membrane receptor or other important binding site. These primary antibodies are then

themselves used as antigen to produce secondary antibodies, some of which will

recognise the binding site on the primary antibody. These are the anti-idiotype anti-

bodies and they have the unique quality that their binding site structurally resembles

the original epitope. They themselves can be used as vaccines as the immune response

raised to them will cross-react with the native original epitope. Some human cancers

have cell surfacereceptorsthat are unique to them and these can be used as a target for

antibody therapy. Anti-idiotype antibodies raised to the cell receptors are used to

immunise the patient. The resulting antibodies made by the patient bind to the receptors

on the tumour cells allowing the immune system to recognise and destroy the tumour.

The method has had some success in the treatment of ovarian and bowel tumours.

7.2.7 Phage display for development of antibody fragments

Bacteriophageorphage, as they are known, are viruses that infect and replicate

within bacteria. They can be engineered by molecular methods to express proteins

and providing the protein sequence is tagged to the coat protein gene then the foreign

protein will be expressed on the virus surface. It is possible to isolate the variable (V)

antibody coding genes from various sources and insert these into the phage resulting

in single-chain antigen-binding (scFv) fragments. Whole antibodies are too large and

complex to be expressed by this system but the scFv fragments can be used for

diagnostic purposes. The DNA used in this process may come from immunised mouse

B cells or from libraries derived from naive mouse (or other species). The V genes are

cloned into the phage producing a library which is then assessed for specific activity.

It is important to isolate clones that have the specific activity that is required and this

can be done by immobilising the antigen onto a solid surface and then adding phage

Hapten not

recognised by

immune system

Hapten

conjugated to

carrier protein

Hapten conjugate

recognised by

immune system

Antibodies made that

recognise conjugate and

also hapten by itself

Fig. 7.7Making antibodies to haptens.

279 7.2 Making antibodies