With the help of clinical trials, Donald Kufe, MD, and his colleagues are working to make their vaccine technique more effective against several cancers.
Unmasking a danger
Cancer cells are masters of camouflage. The surface molecules that identify them as cancerous are, in effect, too muted to attract much notice from the immune system.
As long as cancer cells maintain their low profile, they're relatively safe from attack. Find a way to make their surface markings blaze forth in all their microscopic menace, however, and the immune system will move against them with all the forces at its disposal.
That is what researchers led by Donald Kufe, MD, of Dana-Farber have sought to do with a group of vaccines now in clinical trials.
Their approach involves the use of antigen-presenting cells, which roam the circulatory system and act as the body's customs inspectors. When they encounter another cell, they strip special molecules, called antigens, from the cell and display them on their surface. As a result, the antigens become readily "visible" to the rest of the immune system. If the antigen pattern indicates an abnormal cell, the immune system's T cells hurry in to destroy it.
Kufe (pronounced "Keefe") and his colleagues were the first to develop vaccines by fusing patients' tumor cells with antigen-presenting cells called dendritic cells, then injecting them into patients. The theory was that by unmasking the tumor cells and targeting them for attack, the dendritic cells would stimulate a particularly fierce immune reaction against tumors.
The first round of clinical trials to use the technique demonstrated that the vaccine is active in the treatment of patients with advanced cancers. The trials, conducted at Dana-Farber and elsewhere, have studied the technique's safety and effectiveness in patients with breast cancer, renal (kidney) cancer, melanoma, and brain tumors. "In all four groups, we have seen anti-tumor activity, including partial and complete remissions of tumors, with no toxicity or side effects," Kufe remarks. "The experience of the first trials has led us to believe that we can improve the vaccine."
"With the old method, it took three months, on average, to prepare and produce a vaccine for a patient. Using adenoviruses, it takes just 10 days to two weeks."
— Glenn Dranoff, MD
Already, there are clues. The clinical trials showed the vaccine works best in patients who have not previously had chemotherapy, perhaps because chemo weakens the immune system, leaving the vaccine less to "work with." The Kufe lab and Japanese scientists have discovered that the substance interleukin-12 primes the vaccine to take action. And Kufe and his colleagues are exploring using more mature dendritic cells in vaccines, reasoning that they will perform better than younger ones.
"This work provides a foundation for us to improve the vaccine — to determine who is most likely to benefit and how it can be made more potent," Kufe says. "It's often in this refinement stage that a therapy's true effectiveness is realized."
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