Plants make lectins as part of their defence against insects, and some of these lectins are toxic enough to kill animal cells by stopping them making proteins. They could be used to build targeted cancer drugs by attaching them to monoclonal antibodies that seek out specific cells. The plant protein ricin is the leading toxin for this use.
Diseases caused by abnormal behaviour of particular cells, cancer above all but also autoimmune diseases, are hard to treat with chemotherapy. Successful cancer treatment should remove the abnormal cells while sparing normal ones, which has never been fully achieved. The most successful cancer drugs target rapidly dividing cells, but even at best they still cause serious side effects. So it makes sense to combine a guide that finds the target cells with a powerful toxin: a monoclonal antibody joined to a plant lectin such as ricin, called an immunotoxin.
Ricin comes from castor bean seeds (Ricinus communis). It is easy to purify, rarely triggers an immune reaction in people and is extremely toxic. It is made of two chains joined by a sulphur bond. The A chain is an enzyme that permanently disables the 60S part of the ribosome, stopping protein production (mammalian ribosomes are far more sensitive than plant ones). The B chain binds galactose on the cell surface and helps the A chain get inside the cell.
Two strategies have been used: attaching whole ricin to a targeting antibody (more toxic to cancer cells but less specific), or attaching only the A chain (more specific but less toxic, and harder to purify). Genetic engineering is now used to reduce the liver's uptake of the A chain and the B chain's ability to bind normal cells, reducing harm to healthy tissue while keeping the toxin's ability to enter the target cells. These proteins are produced in E. coli bacteria using recombinant DNA technology.
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