A precise calibration
The ideal cancer vaccine would give the immune system a license to hunt only cancer cells. Unleashing a wider attack is risky because it might engulf healthy cells as well as cancerous ones.
One solution would be to identify features that are unique to cancer cells and can be recognized by the immune system.
Researchers are developing a set of tumor antigens that could eventually help treat all human cancers.
At Dana-Farber, a search began six years ago for molecules that are located in cancer cells but not, for the most part, in normal cells, and that the immune system has not previously encountered. Introducing these molecules — called universal tumor antigens — to the immune system would be the equivalent of tossing a thief 's sweaty handkerchief to a pack of bloodhounds. The immune system would focus its energies on tracking down and destroying tumor cells bearing those antigens.
Dana-Farber's Lee Nadler, MD, and his colleagues Robert Vonderheide, MD, PhD, and Joachim Schultze, MD, identified two such antigens. One is called hTERT, a molecule discovered several years ago by Matthew Meyerson, MD, PhD, then of the Massachusetts Institute of Technology and now of Dana-Farber. The other is called CYP1B1.
Experiments are under way to determine if either of these molecules can be used in cancer vaccines. Vonderheide (who is now at the University of Pennsylvania Cancer Center) pioneered a technique involving hTERT currently being tested by Dana-Farber's Nicholas Haining, MD. In the technique, doctors vaccinate patients with a small piece of hTERT known as a peptide in hopes of sparking an anti-tumor response.
An alternative method, also being studied, is to mix the peptide with patients' dendritic cells, revealing the peptide to the immune system. Clinical trials have shown that both techniques are safe for patients, while laboratory work indicates that the immune system does react to the peptide's presence.
John Gribben, MD, DSc, is conducting vaccine clinical trials at Dana-Farber.
Another set of experiments involves the molecule CYP1B1. The Institute's John Gribben, MD, DSc, in conjunction with Zycos of Lexington, Mass., is conducting a study in which it is given to patients as a "DNA vaccine." The vaccine is injected into patients and causes their cells to produce the CYP1B1 antigen. This is especially true for antigen-presenting cells, whose role is to alert the rest of the immune system to disease. According to Gribben, the trial is going well, and the vaccine hasn't produced any side effects.
Nadler, Gribben, and Haining are developing a panel of universal tumor antigens that eventually may serve as targets for treating all human cancers. They plan to test techniques for making these antigens particularly visible to the immune system.
Says Nadler, "We are uniquely positioned to accomplish this goal. In the next several years, we hope to combine these strategies in patients to 'mop up' residual cancer cells that remain after surgery, radiation therapy, and chemotherapy. The real promise for immune-based therapy is to attack the last remaining cells. This may bridge the gap between treatment and cure."
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