Clay Siegall develops ingenious method for producing monoclonal antibodies

In the early 1990s, a man named Clay Siegall devised an idea that would allow for the delivery of highly lethal cytotoxins to the site of malignant tissues. This was an extremely important development due to the fact that it potentially would eliminate completely the side effects associated with chemotherapy, which were oftentimes responsible for some of the most severe side effects of any drug known to man, including death.

While working as a senior researcher at Bristol-Myers Squibb, Dr. Siegall and his team began devising a way to use human antibodies to deliver chemotherapeutic agents directly to malignant tissues, bypassing the need for systemic release of highly lethal poisons into the patient’s system. The means by which Dr. Siegall at his team synthesized these antibodies had never been attempted before.

The crucial insight came from the fact that mammals will produce antibodies to any foreign tissue introduced into their body. Using this idea, Dr. Siegall was able to inject mice with malignant tissues of various types of cancer, causing an immediate reaction in the mouse’s body which produced large numbers of antibodies. While these antibodies were rarely ever effective in treating highly malignant cancers, they were almost invariably effective at creating a molecular key that would allow the antibody itself to seek out and then latch onto the malignant tissue. Dr. Clay Siegall hypothesized that if he could use these antibodies as a vehicle to deliver a cytotoxin, he could completely avoid the systemic release of large amounts of poison into a patient’s bloodstream.

Dr. Siegall and his team then created methods by which they could synthetically alter these antibodies by ever-so-slight means, creating thousands of antibodies they could test for the minimal allergic response in human subjects. By this means, they were able to create hypoallergenic antibodies that served as vehicles to which lethal cytotoxins could be bound, directly delivering the payload to the site of the malignancies.

Today, these so-called antibody drug conjugates are among the most innovative and promising new drugs in the arsenal that oncologists have at their disposal in the fight against cancer.


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