Putting Bull's-Eyes on Cancer Cells


One day a decade ago, Dr. Philip Low's daughter, Emily, who had measles at the time, sneezed in his face -- and the Purdue University researcher had an epiphany. "I realized that I inhaled half a million measles molecules, but I wasn't fearful," Low recalls. The reason: He had been vaccinated against the disease. He wondered if a modified vaccine would work in cancer patients -- even after tumors were well-established.

Now, Low and a team of scientists at Endocyte Inc., in West Lafayette (Ind.) have come up with a new type of cancer vaccine. Its general concept is nothing new, but it uses a pathway to destroying malignant cells that's at the forefront of cancer immunotherapy. By combining the vaccine with a type of vitamin called folate, researchers are getting cancer cells to accept the key to their own destruction. This substance is a carrier for the vaccines, Low says. "It's like feeding a dog heartburn medicine in a glob of peanut butter, and in the process he swallows the pill."

SPOTTING THE ENEMY. The two-step process works by flagging cancer cells and making them more recognizable to the body's natural attack force, the immune system. "Cancers survive because the body views them as normal tissues," permitting them to multiply unrestrained, says Low. The trick is to tag cancer cells, wherever they are, so they can be spotted by the immune system or targeted by drugs.

Low and the Endocyte team use a dye called fluorescein as their tag. Injected into a mouse, it prompts the animal to produce antibodies that can recognize the dye. Once that happens, the immune system recognizes fluorescein.

Next, the team attached the conspicuous fluorescein molecules to folate, which acts as the "glob of peanut butter" that delivers the dye to cancer cells. Folate is a form of vitamin B that certain types of cancer cells -- including lung, ovarian, and kidney tumors -- capture and display on their surfaces. When the same mouse is injected with the combined fluorescein-folate molecules, the tumor cells also end up wearing the immunogenic dye, which means that the immune system can spot and destroy them.

NOT ALWAYS EFFECTIVE. In a study described in the May issue of the Journal of Cancer Immunology & Immunotherapy, the technique cured more than 200 mice with advanced metastatic lung cancer. Low's team plans to test the approach in human clinical trials this fall. To cancer patients, nothing is scarier than metastasis -- the spread of malignant cells, often signaling that the cancer can't be cured. Retargeting the immune system using this technique may stop metastasis.

The strategy, however, can't work on all cancers. Imagine that folate is a key. Some cancer cells have a groove called a folate receptor that acts like a lock. Only tumor cells that have folate receptors can be targeted. Roughly 30% of cancers -- ovarian, kidney, most brain, some types of lung cancers, and half of breast cancers -- have folate receptors, but most colon cancers and prostate cancers do not. And while researchers have shown that folate delivers a dose of fluorescein to cancer in mice, it may not have the same strength in human beings.

So, it's far from certain that folate targeting will prove effective in clinical trials. Indeed, a similar idea -- vaccines for melanoma -- created headlines earlier this year but has produced no conclusive data. If results point to efficacy in humans, though, Endocyte's approach could be a significant advance in cancer vaccines. By Aliya Sternstein in New York


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