To retarget the immune system, scientists first inoculated mice to raise antibodies against a hapten (a small, inert organic chemical) called fluorescein. Once high levels of the antibodies were circulating throughout the rodents' systems, cultured cancer cells were injected. Tumors were allowed to establish themselves and spread throughout their hosts. Normally this would cause death in 21 days, however, the mice that were injected with the folate-fluorescein conjugate eight days after the injection of cancer cells lived well beyond 120 days (a point at which the animals were considered to be cured).

Another part of Endocyte's technology stems first from its ability to diagnose cancer. In order to determine which cancers have folate receptors and, therefore, are receptive to a folate-related treatment, cancer must be detected by using a folate-related diagnostic procedure Endocyte developed called FolateScan. This diagnostic method now is being tested in Phase I/II FDA-regulated human clinical trials.

To diagnose cancer, another type of "beacon" this time a radioactive imaging agent is attached to the folate. FolateScan is administered intravenously to patients. When nuclear imaging of the patient shows that the radio-labeled folate conjugate has concentrated in an unknown mass, it tells researchers that the mass has folate receptors and that the tissue is malignant. More importantly, it means that the cancer detected is the type that may be receptive to a folate-related therapy.

Researchers initially used the radioactive agent indium to detect folate-receiving cancers, but then developed a new diagnostic approach with technetium. Technetium decays more rapidly and decreases the patient's exposure time to the radioactive agent from one month to two days. The shorter half-life of technetium also allows researc
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Contact: Jeanine Phipps
jeanine@purdue.edu
765-496-3133
Purdue University
20-Jun-2002