Activate dendritic cells turn on biological clock

A molecule specially modified by researchers at Baylor College of Medicine can reset the biological clock for cancer vaccines, potentially making them more potent.

In a report that appears online in Nature Medicine, Dr. David Spencer and colleagues describe their method of delaying the time at which crucial dendritic cells are activated by the immune system. This prolongs the time during which the cancer vaccines can undertake their task, he said.

Dendritic cells are important because they present to the immune system the proteins or antigens that cause the immune system to go into action. They are key to cancer vaccines that seek to alert the immune system to presence of cancer by making it aware of tumor antigens or proteins that are unique to that malignancy.

"Once you activate dendritic cells, you turn on a biological clock," said Spencer, an associate professor of immunology at BCM. "Dendritic cells have a finite life span after they are activated."

The makers of cancer vaccines would like to activate the dendritic cells, expose them to the tumor antigens and then reinject them into patients. Once in the body, they would migrate to the lymph nodes where they interact with specific immune system operatives called T-cells, activating them to attack the cancer. However, the process can take as long as a day, reducing the period during which the dendritic cells are active and can accomplish their work.

However, using a drug that results in the linking of two identical molecules (a process called dimerization), Spencer and colleagues found that they could wait until the dendritic cells got to the lymph nodes to activate them. That significantly extends the period during which the cells can remain active and, in turn, activate the immune system's T-cells.

Spencer steered graduate student Brent Hanks toward manipulating dendritic cells, but credits Hanks with settling upon a molecule called CD40 that could be used to activate the dendritic cells after they reached the lymph nodes.

"This was a key decision, since CD40 is likely the most potent activation molecule on these cells," he said. "Our dendritic cells live longer in the lymph nodes and we think they are more potent when the get there."

"We think because of the special attributes of this approach, it should have a better chance of working in patients whose immune systems are already attenuated by disease or prior treatment and should be complementary to other approaches already out there," said Spencer.

Others who participated included Drs. Kevin M. Slawin, Rana A K Singh, Michael Barry, Jianghong Jiang, and Weitao Song, all of BCM.

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