Cellular switch
The standard advice for people newly diagnosed with chronic lymphocytic leukemia (CLL) is to "watch and wait" — have their condition monitored until it progresses and specific symptoms begin to show. Even then, medication can only control, not cure, the disease.
"The real promise for immune-based therapy is to attack the last remaining cells. This may bridge the gap between treatment and cure."
— Lee Nadler, MD
The CLL vaccine currently undergoing a clinical trial led by Gribben is more ambitious. It seeks to send the disease into permanent remission, offering patients a new alternative to chemotherapy, the mainstay of current treatments.
Instead of trying to clue in the immune system to the presence of molecules that exist only on cancer cells, the vaccine attempts to outfit CLL cells with a molecular "switch" they don't normally possess.
"One way to think of leukemia is as a cancer of the immune system," Gribben states. "Normal white blood cells have a 'ligand' — a surface molecule called CD40 — that switches on the immune system's response to disease. When those cells are leukemic, the CD40 switch is missing."
To restore it, Gribben's technique uses a retrovirus that carries the DNA instructions for producing CD40. The vaccine is made by taking a blood sample from a patient and mixing leukemic blood cells with the retrovirus. The retrovirus inserts its DNA into the cells, causing them to manufacture the CD40 ligand. Patients receive 10 injections of the vaccine over several months.
The results of the Phase I trial are promising, Gribben reports. "All of the participants experienced a drop in their white blood cell counts after one vaccination," he says, a key sign that the immune system had responded to the vaccine. Although the levels later rose, Gribben hopes the regimen will prove more effective in a similar trial at DFCI, Brigham and Women's Hospital, and Massachusetts General Hospital.
"Future trials will help us determine if the immune response sparked by CD40 is enough to cure the disease, or if it will find a way of returning."
