Cancer patients and physicians are always looking for therapies free of side effects. But the standard treatments available to them -- chemotherapy and radiation -- typically work via a shotgun approach, indiscriminately killing all rapidly dividing cells whether they're cancerous or not. A long-held notion that the immune response might, in some practical manner, be harnessed to target cancer cells while sparing the rest is now being put to the test.
An experimental vaccine is now in multi-center, late-stage trials for treatment of glioblastoma, the most common brain cancer in adults. If the therapy lives up to its promise, it could potentially be used for other cancers as well.
Glioblastoma, which strikes more than 10,000 adults per year in the United States, is a particularly aggressive form of brain cancer: Only one-half of patients survive for one year, even after radiation treatment and surgery to remove as much of the tumor as possible. The recent introduction of temozolomide, a chemotherapeutic drug, to the arsenal has added barely two months of survival to patients' lives.
Normally, we think of vaccines as prevention measures that enable our immune systems to pounce on bacteria or viruses the minute they strike. In this case, however, the new vaccine -- which goes by the experimental name CDX-110 -- is designed to kick-start an immune assault on an existing tumor.
So far, CDX-110 has been administered to almost 70 people, with virtually no side effects, according to Dr. John Sampson, a neuro-oncologist and brain surgeon at Duke University in Durham, N.C., who has been working on the vaccine.
The vaccine is designed to treat a certain subtype of glioblastoma that is present in 25% to 40% of cases. Tumors of this sub-type have a mutant protein known as EGFRvIII studded on the surface of many of their cells -- a twisted variant of a normal protein called EGFR. The normal EGFR is widely distributed on cells in the body and will stimulate division of the cell when it receives the correct hormone signal.
The mutant protein EGFRvIII, however, has an altered structure that sticks it in the "on" position permanently -- relentlessly triggering cell division, causing out-of-control, cancerous growth. Glioblastoma patients testing positive for EGFRvIII have a bleaker prognosis than those who don't. Virtually no EGFRvIII-positive patient survives two years, versus about 15% of those who are negative.
But there's an upside. The very uniqueness of the EGFRvIII protein has allowed scientists, in theory, to design a vaccine against tumor cells and only tumor cells.
The vaccine, designed by Sampson and Dr. Amy Heimberger, a brain surgeon at the M.D. Anderson Cancer Center in Houston, is fairly simple: It consists of a small fragment of EGFRvIII with a slight structural modification plus a couple of substances known to enhance the immune response. The theory: The body's immune cells, after being exposed to this protein, will launch an attack on EGFRvIII-positive cells but -- unlike chemotherapy or radiation -- will spare hair, skin, intestinal lining and immune cells.
In a just-completed study led by Sampson and Heimberger, 23 glioblastoma patients underwent radiation treatment and then surgery to excise all but traces of their tumors, followed by a single dose of the anti-tumor drug temozolomide.
Next, they received three biweekly injections of the experimental vaccine. Vaccine injections were continued monthly until patients' tumors returned, as they almost invariably do.
The results, which are not yet published, were encouraging, Heimberger says. Half of the patients survived for more than 30 months after treatment, versus the 12 months expected for patients treated only with radiation and surgery. And 65% were still alive after two years, compared with the almost-zero two-year survival rate predicted for this class of patient. Several have survived more than three years, Heimberger adds.
Typically, tumors recur within six months in patients given standard treatment, but with vaccine treatment, recurrence was delayed almost 15 months, Sampson says.
CDX-110 is not the only cancer vaccine in clinical trials, but it may be the first truly tumor-specific one that can be easily mass-produced. (A few other "personalized" vaccines, which aim at protein targets that differ from one patient to the next, are also under clinical investigation, but identifying and manufacturing vaccines on a one-off basis is inherently costly.) The prospect of a first-ever "off the shelf" cancer vaccine applicable to large numbers of patients has drawn the attention of investors as well as investigators.
