Ricin - Plant Toxin Used as Immunotoxins,Endocytosis,Toxicity Effect,Chemotherapy,Tumour Cells

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	Ricin - Plant Toxin Used as Immunotoxins - Ricin is a toxin polypeptide (A chain) and is attached to a cell binding polypeptide a lectin (8 chain) which binds to glycoproteins or glycolipids (containing galactose), present on the cell surface. The cells are thus recognized by 8 chain and the immunotoxin enters the cell by a mechanism not fully understood (perhaps receptor mediated endocytosis). The A chain (ricin) then inhibits protein synthesis by enzymatically inactivating the EF2 binding portion of 60S ribosomal subunit. It has been shown that in this immunotoxin, the 8 chain can be replaced by any binding moiety such as a hormone, a growth factor or an antibody, so that the binding specificity is changed, but the toxicity effect is retained.
The immunotoxin 'ricin' has actually been used for a study of its effect on mouse tumour cells (8' cell tumours). There can be a variety of these tumour cells each having its own characteristic ideotype (specific immunoglobulin or surface antigen), so that an anti- ideotypic antibody can by raised and conjugated with the toxin (ricin or ricin A, which is a chemically synthesized toxin resembling natural ricin) to give an immunotoxin. When tumour cells were incubated with such an immunotoxin, protein synthesis decreased by 70-80%, while the protein synthesis in control cells had no effect. Further, if the tumour cells had a different ideotype (different specific immunoglobulin, for which the antibody present in immunotoxin is not an anti-ideotype), then no effect of the immunotoxin was observed.
Experiments have also been performed on bone marrow cells (treated with immunotoxin) used for reinfusion into a patient treated with high doses of irradiation or chemotherapy leading to complete killing of the patient's own bone marrow. Such infusions, did not develop tumours, since the reinfused cells were pretreated with immunotoxin to kill tumour cells, if any present. In vivo experiments were also conducted with mice to study the effect of immunotoxin for cancer therapy. It is believed that these immunotoxins and other types of drug designing will find increasing application in future therapeutic uses for cancer treatments.