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Thursday, July 08, 2004

Antibody directed antidotes

Some doctor/scientists especially my father Thomas Waldmann (who also takes nice photos which no one is viewing) use antibodies to cancer specific antigens to direct toxins or, in practice, alpha and low energy beta emitting radionuclides to tumours or leukemias. A problem with non radioactive toxins is that they last too long with a half life as long as or longer than the half life of the attachment to the antibody. Thus they end up harming healthy organs e.g. the liver. I just had a thought. Antibody antigen complexes can be very very tight. Toxins can be inactivated essentially forever by appropriate anti-toxin antibodies. How about directing the anti-toxin to the healthy organ which is damaged by the therapy ? If you can get the victim organ decorated by anti-toxin, you maybe could protect it. This would require a bifunctional antibody fusing the anti-toxin with an antibody specific for a surface antigen of the organ at risk. The surface antigen has to be one which uhm stays on the surface and doesn’t cycle into lysosomes or something. The bifunctional antibody would have to have a partly deleted fc so that it doesn’t fix complement or act as a signal for antibody dependent cellular cytotoxicity.

Why not ?

Actually, antibody directed anti-toxins could be more generally useful. Standard chemotheraputic agents kill cells as they divide. Thus they kill cancerous cells, bone marrow, the lining of the digestive system and hair follicles. I wonder if it is possible to make a bifunctional antibody with one bit that binds to bone marrow stem cells and the other which binds irreversibly to, say, methotrexate. Thus any methotrexate which found it’s way into the bone marrow would be inactivated one hopes until it is excreted/processed in the liver.

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