Ricin drugs

Raso, V., and Basala, M. (1985) Study of the transferrin receptor using a cytotoxic human transferrin-ricin A chain conjugate. In Receptor-Mediated Targeting of Drugs, (G. Gregoriadis, ed.), Vol. 2, p. 73. Plenum, New York. 

Vitetta, E.S., and Thorpe, P.E. (1985) Immunotoxins containing ricin A or B chains with modified carbohydrate residues act synergistically in killing neoplastic B cells in vitro. Cancer Drug Deliv. 2, 191. 

Drugs Available (No specific anti-toxin) Active immunization and passive antibody prophylaxis are under study, as both are effective in protecting animals from death following exposure by intravenous or respiratory routes. Ricin is not dermally active therefore, respiratory protection is the most critical means of prevention. 

Clinically, monoclonal antibodies are also proposed as drug delivery vehicles in certain tumors where specific tumor-associated antigens are expressed. In this context, investigators have found that by conjugating toxins such as the A chain polypeptide of the plant protein ricin or the bacterial toxin from Corynebacterium diphtheriae to monoclonal antibodies specific for certain tumor type, as few as one or two molecules of antibody-toxin conjugate can destroy a tumor cell in vitro. Some success has also been obtained in clinical trials with monoclonal antibody-toxin conjugates. 

Cytotoxic drugs including toxins such as saporin, ricin A chain, vinca alkaloids, and radioisotopes have been delivered to tumour cells with BsMAbs that bind to the drug/toxin with one arm and to a surface molecule on the targeted cell with the other arm. This approach has proven successful in animals as e.g. shown by Schmidt et al. [78]. 

Many attempts have been made to link monoclonal antibodies specific for antigenic determinants on cancer cells to protein toxins such as ricin (Box 29-A). It is hoped that this may provide an effective way of carrying toxins into cancer cells/ 1 r Therapeutic human monoclonal antibodies are already in use as antirejection drugs for kidney transplantation, for treatment of rheumatoid arthritis, Crohn disease, and for some types of cancer/... 

As with some of the other chemicals discussed in this book, the possibility of using ricin as a drug, in particular for the treatment of cancer, has been explored. The possibility of attaching the part of the toxin that is lethal to cells, to antibodies, which would then target cancer cells, is being studied. 

Hazard is the inherent ability of the substance to cause an adverse effect, that is its toxicity (for example, dioxin and ricin are known, potent poisons). Exposure is the level of the substance in the air, water, or food or the dose of a drug. 

The mid-spectrum region between chemical and biological agents includes substances such as bioregulators and toxins. These are all chemicals and almost all are not included in the Schedules - the two that are listed in Schedule 1 are ricin and saxitoxin. These mid-spectrum materials can now be readily produced in quantity -and for prohibited purposes, impurities are not a problem. The challenge to the Convention posed by such materials is further increased by the recent advances in drug-delivery techniques. 

N. J. Mantis, Vaccines against the category B toxins Staphylococcal enterotoxin B, epsilon toxin and ricin, Advanced Drug Delivery Reviews, 57, 2005, 1424-39. 

General supportive measures are likely to be effective in therapy of intoxication. Artificial ventilation could be lifesaving in the case of neurotoxins such as the botulinum toxins and saxitoxin. Oxygen therapy, with or without artificial ventilation, may be beneficial for intoxication with toxins such as ricin that directly damage the alveolar-capillary membrane of the lung. Vasoactive drugs and volume expanders could be used to treat the shocklike state that accompanies some intoxications (eg, with staphylococcal enterotoxin B). These measures could be used in conjunction with more specific therapies. 

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