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Getting Personal

Researchers attack patients' tumors with custom-tailored vaccines.

BY KATY HUMAN
PUBLISHED THURSDAY, MARCH 4, 2010
In 2003, Stephen Creel, a manager at a software company in Austin, Texas, suddenly started passing blood in his urine. He had just celebrated his 40th birthday with friends and his wife, who was pregnant with their daughter, and he was as fit as he’d been in years.

The diagnosis of kidney cancer—renal cell carcinoma—was “shocking,” Creel says.

His father-in-law, a cancer researcher, directed Creel to M.D. Anderson Cancer Center in Houston, almost 170 miles away, where oncologists were testing an experimental vaccine to treat kidney cancer. 

They surgically removed patients’ tumors, sent samples away for processing, and then re-injected cancer-specific proteins back into the patient. They were trying to activate the patients’ own immune system cells, train them to recognize cancer as an invader, and fight it off. 

“I really liked the idea of that, getting your body to do the work, not just chemicals,” Creel says.

Preventive vaccination, also referred to as immunization, has become a critical part of global public health. Since the body has a much easier time developing immunity against foreign proteins that come from viruses or bacteria, vaccines to prevent cervical and liver cancers (associated with viral infection) are already available. But tricking the body into fighting existing cancer has proved more complicated because most cancer cell proteins are similar to normal proteins, and the body is “educated” not to develop immunity against its own proteins. Nonetheless, treatment vaccines for prostate cancer, lymphoma, melanoma, and other cancer types are undergoing late-phase tests in people, and the results are inspiring restrained optimism. 

“We’re training the body to reject the tumor,” says Leisha Emens, MD, PhD, a breast cancer researcher and vaccine developer at Johns Hopkins University in Baltimore. The immune approach is unlike new types of chemotherapy, radiation, or hormonal therapy, Emens says. Treatment vaccines target cancer cells more precisely, have far fewer side effects, and may be less likely to foster drug resistance. “This works completely differently,” Emens says. “With immune-based therapy, you’re actually changing how the body responds to cancer.”

Emens and other cancer vaccine researchers caution that it could be years before clinicians routinely use this immunological approach to treat cancer. Scientists have been experimenting with the technique for decades, and have tripped over many obstacles. One of the most fundamental: The immune system discriminates “self” from “nonself” at a basic level. Viral or bacterial infections are “nonself” and perceived as a threat, but cancers come from the body’s own tissue, so the immune system generally develops “tolerance” and recognizes cancer cells as “self,” and does not respond.

But as scientific understanding of the complex immune system has grown, many of those obstacles are falling away. Today, the Food and Drug Administration is considering data from a phase 3 clinical trial of a vaccine against metastatic prostate cancer called Provenge (sipuleucel-T). The FDA will decide whether to approve the vaccine by May 1.

“This is such an exciting time to be in the field of cancer vaccine research,” says James Gulley, MD, PhD, director of the clinical trials group within the Laboratory of Tumor Immunology and Biology at the National Cancer Institute. “We’re on the verge of having approved an entirely new approach to cancer treatment.”

In 1891, New York doctor William Coley was frustrated by the deaths of patients with metastatic bone sarcomas. He pored over the literature of the time, and found reports that sarcomas sometimes disappeared in patients who suffered unrelated bacterial infections.

“Coley began injecting different types of bacteria, anything into tumors, to trigger an immune response,” Gulley says. Anecdotally, the technique worked on occasion: “Coley’s toxins” appeared to activate patients’ immune systems against cancer as well as bacterial invaders (the immune system sometimes “cross-reacts” with a broader set of proteins than the triggering infection).

But when researchers began conducting carefully controlled clinical trials with cancer vaccines, many simply didn’t work. Part of the reason may have had to do with patient selection, Gulley says. “We started testing these therapies in patients who failed everything else and have no other options. They’ve had every other poison around. They have very advanced disease. So when vaccines were tried, lo and behold, there wasn’t a lot of activity.”

Even in the past few years, a few high-profile “failures” diminished some hope for the technique. A much-discussed vaccine against melanoma known as Canvaxin showed no benefit, and a phase 3 trial for the vaccine Oncophage (vitespen) delivered mixed results in kidney cancer: One specific group of patients with stage 1 or 2 disease saw significant improvement in recurrence-free survival, but there was no positive effect when all study participants, including later-stage patients, were evaluated as a group.

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