Health & Medicine / Vaccines

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Two centuries ago Edward Jenner administered the first scientifically developed vaccine, injecting fluid from a dairymaid’s skin lesion into an 8-year-old boy. The English physician knew that dairymaids who contracted cowpox, a comparatively mild skin disease, became immune to the much deadlier smallpox, which at the time killed 400,000 Europeans a year. Jenner hoped the fluid from the cowpox lesion would somehow inoculate the boy against the smallpox scourge. 
His hunch proved correct. Today vaccines (vaccinia is Latin for “cowpox”) of all forms save 3 million lives per year worldwide, and at a bargain price. A measles shot, for instance, costs less than a dollar per dose.

By training the human immune system to recognize and ward off dangerous pathogens, vaccines can protect against disease for decades, or even for a lifetime. Preventive vaccines work by introducing harmless microbial chemical markers, known as antigens, which resemble the markers on living microbes. The antigens train the immune system to recognize and destroy those microbes should they ever appear in the body. By injecting cowpox antigens into his patients’ bloodstream, for instance, Jenner primed their immune systems to attack the similar smallpox virus.

Today medical scientists are taking 
Jenner’s ideas in new directions. They are exploiting a growing understanding of the immune system to develop therapeutic vaccines: ones aimed not at preventing infection but at rooting out established disease or even changing how the body functions. In the spring of last year, the FDA approved Provenge, a vaccine that beats back prostate cancer and is the first of the new generation of therapeutic vaccines to go into widespread use. That may be the trickle before the flood. A 2010 survey by the market analysis firm BCC Research identified 113 therapeutic vaccines in development, many already in human trials.

THE CANCER SHOT


With a near-endless supply of patients willing to undergo novel treatments, cancer researchers have been among the most aggressive in experimenting with therapeutic vaccination. “Cancer vaccines are the stalking horses for therapeutic vaccines,” says cancer immunologist Lloyd Old. Based at the Cancer Research Institute in New York, Old is the director of the Cancer Vaccine Collaborative, an international program dedicated to fighting cancer from the inside out.

Much of the Collaborative’s work is based on Old’s pioneering studies of the immune system over the last half-century. His research built on the insights of 19th-century surgeon and cancer researcher William Coley, who noticed that for then unknown reasons, postoperative cancer patients with severe bacterial infections often experienced complete remission. In 1891 Coley took the first steps toward cancer immunology when he began intentionally injecting late-stage bone cancer patients with Streptococcus bacteria, which cause strep throat. The injections shrank tumors, but the resulting infections killed two of his patients. He then tried injecting a combination of heat-killed bacteria, a mixture that became known as Coley’s toxin. Although it remained controversial, Coley’s cancer vaccine was widely used until radiation and chemotherapy became standard treatment in the 1940s.

By the time Old began his cancer research, in the 1950s, Coley’s toxin had been relegated to the American Cancer Society’s “black book” of suspected quackeries. “Coley’s vaccine was in such disrepute in large part because no one could explain how it worked,” Old says. Nevertheless, he became fascinated with Coley’s promising results, especially after hearing reports of mouse tumors shrinking after injections of zymosan, a yeast extract. Tumors in those animals continued to grow for close to two weeks after the injections but then started to disappear.

“Clearly the zymosan was not killing the tumors directly,” Old says. “Instead it affected the host in a way that triggered a tumor-clearing response.” He spent much of his career investigating ways the immune system can clear the body of cancer. In the process he identified one of the first recognized cytokines, or immune signaling molecules. Cytokines direct the biochemical conversation that immune cells use to coordinate their activities. Old’s insights suggested that Coley’s toxin worked because it tricked the body into releasing a flood of cytokines by exposing the immune system to what seemed like an enormous bacterial attack. The cytokines then directed an immune response to the bacteria, an onslaught that also killed cancer cells.

Many of the cancer vaccines in development today tap into our current understanding of how dozens of these cytokines help coordinate an effective cancer-clearing response. (The much-publicized HPV cancer vaccine works in a more traditional style: It primes the immune system to fight off human papillomavirus, which can cause cervical cancer.) To make the Provenge prostate cancer vaccine, biochemists at Seattle’s Dendreon Corporation extract a sample of a patient’s own immune cells and bathe them in a chemical soup of prostate cancer antigens that are chemically linked to a cytokine that screams, “Attack this!” The activated immune cells are then injected back into the patient’s body to spread the call to arms.

In the study of 512 prostate cancer patients that led to Provenge’s approval, one-third of the vaccinated patients remained alive after three years, compared with one-quarter of those who received a placebo shot, for an average life extension of four months. Old is hopeful the next wave of cancer vaccines can improve those numbers. The Cancer Vaccine Collaborative is working on treatments that target multiple cancer antigens, which should trigger a more aggressive immune response and increase the odds of defeating tumors.

Potential patients: 1.5 million Americans are diagnosed with cancer each year.