Biologics

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8. Example - Fusion proteins

Fusion proteins are a fairly recent type of biologic therapy, made by joining together different proteins (or parts of proteins) to make a novel molecule. Each of the different component parts of the fusion protein may occur naturally, but the final medicinal product is made only in the laboratory.

Fusion proteins are produced in the same way as other biologic medicines. Sequences of DNA are constructed to produce the entire fusion protein, and these DNA sequences are transferred into living cells that are grown to produce large quantities of the required protein.

By joining together different proteins that have different beneficial qualities, the potency, stability and specificity of fusion proteins can be greatly enhanced compared with naturally occurring proteins. Two types of fusion protein, receptor fusion proteins and peptibodies, have been developed for therapeutic use and other novel variations are being studied.

Receptor fusion proteins join together one or more receptors with part of a naturally occurring antibody. The receptors give the fusion protein its specificity and carry out the desired therapeutic function. For example, the receptors bind to a disease-causing protein and stop it from working and the antibody fragment improves the stability of the molecule (i.e. it increases the amount of time that receptor fusion proteins stay in the body before they are inactivated).

Peptibodies consist of a protein component (or part of a protein, a peptide: ‘pepti-‘) and an antibody-like component (‘-body’). The protein component is the functional part of the peptibody and binds to cells or other proteins to exert its therapeutic effects. As with receptor fusion proteins, the antibody component increases the stability of the molecule as a whole.

An even more recent class of fusion protein joins together two different antibodies. Each of the antibodies attaches to a different type of cell, bringing the two cells into close proximity of one another. In one example, the fusion protein brings together a cell from the immune system with a cancer cell, resulting in the cancer cell being killed by the immune cell.

Similarly to monoclonal antibodies, fusion proteins are likely to be relatively large molecules that require a complex manufacturing and purification process. Fusion proteins are delivered by injection into a vein. The number and frequency of infusions will depend on the fusion protein given and the disease being treated.

Fusion proteins are used to treat a wide variety of diseases, including osteoporosis, cancer and non-cancerous blood disorders. Given their specificity, the number of side effects against cells or organs that are not targeted by the fusion protein should be limited. The targets of fusion proteins involved in disease, however, may also have important functions elsewhere in the body, and so each fusion protein will have its own list of specific side effects. General side effects of fusion proteins are related to allergic reactions to the medicine, and can cause symptoms including fever, rash and headache.