Immunotoxins as Drugs, Gene Fusion, Toxic Peptide, Cytotoxic Drugs, Bacterial Toxin

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Your Ad Here	Immunotoxin as Drugs By creating novel gene fusion using sequences coding for antibodies and toxic peptides, it may be possible to create cytotoxic drugs or magi bullets called immunotoxins. These drugs will attack specific targets in the patients. Some success in this direction has already been achieved in the synthesis has already been achieved in the synthesis of an immunotoxin using a toxic peptide which has properties similar to those of melittin. Immunotoxins are conjugates of cell binding antibody or antigen, covalently bound to a plant or a bacterial toxin, so that when an immunotoxin is supplied to a patient, the antibody or antigen helps in recognition of the target cells to be killed and the toxin component helps in killing thee cells, which may be harmful being cancerous. Thus an immunotoxin will have two parts: (i) a toxin polypeptide or a part of it having toxin activity; this may be called A chain and (ii) a cell binding recognition polypeptide (or antibody or a part of it having binding site), which may be called B chain. These immunotoxins represent a new approach to pharmacology.
Ricin, a plant toxin used as immunotoxin Rice is a toxin polypeptide (A chain) and is attached to a cell binding polypeptide – a lectin (B chain) which binds to glycoproteins or glycolipids (containing galactose), present on the cell surface. The cells are thus recognized by B 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 B 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 (B 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 be 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 in control cells was not affected. Further, if the tumour cells had a different ideotype (having a different specific immunoglobulin, for which the antibody present in immunotoxin is not an anti-ideotype), then no effect of the immunotoxin was observed even in the tumour cells.	Your Ad Here
Experiments have also been performed on bone marrow cells (treated with immunotoxin) used for reinfusion into a patient treated with high dose of irradiation or chemotherapy leading to complete killing of the patient’s own bone marrow. Such infusions did not develop tumour cells, if any present. In vivo experiments were also conducted with mice to study the effect of immunotoxins for cancer therapy. It is believed that these immunotoxins and other types of drug designing will find increasing application in future therapeutics used for cancer treatment

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