STORY OF CALICHEAMICIN

STORY OF Calicheamicin

was discovered in 1981 (or 1987) by a scientist from Lederle Labs (now Wyeth) while on vacation in Kerrville, Texas (Other sources site Waco, Texas). The scientist collected a soil sample, which consisted of caliche clay, and sent it back to the lab for testing. Scientists grew a culture of the soil sample and found tiny bacteria within the sample produced a compound called "calicheamicin". Calicheamicin was found to be an incredibly potent cytotoxic agent and worked by destroying the DNA of cancer cells. Calicheamicin was so potent that it also destroyed the DNA of normal cells (1,000 to 10,000 times more cytotoxic to normal cells than drugs already on the market)..

 Dr. George Ellestad, Dr. Janis Upeslacis and Dr. Philip Hamann (Wyeth) began studying calicheamicin in order to better understand its mechanism. Together, they devised a plan to link calicheamicin to an antibody that specifically targeted cancer cells. In this way, they were able to keep calicheamicin from destroying normal cells because the antibody linker served as a "by pass" taking calicheamicin directly to the cancer cell.

 The FDA approved this new antibody-linked calicheamicin gemtuzumab ozogamicin. (go)) on May 17, 2000, almost 20 years after its discovery.

IT  is the very first drug in its class (antibody-targeted chemotherapy agents) and is used in the treatment of acute myelogenous leukemia. Remission rates of greater than 30% have been reported (Clinical Trials).

However, its effectiveness in early relapsing  LESS THAN 6 months or refractory AML patients is limited, possibly due to calicheamicin being a potent MDR1 substrate

Toxicity, including myelosuppression, infusion toxicity, and venoocclusive disease, can be observed with gemtuzumab ozogamicin.

Pretreatment with glucocorticoids can diminish many of the associated infusion reactions. Studies are examining this treatment in combination with chemotherapy for both young and older patients with previously untreated AML.

This agent has been withdrawn from the U.S. market at the request of the U.S. Food and Drug Administration due to concerns about the product's safety and clinical benefit as shown in trials subsequent to those leading to its accelerated approval.