editors@fiercevaccines.com, April 8, 2010, by Maureen Martino  –  There are already several cancer vaccines nearing FDA approval. Dendreon’s prostate cancer vaccine Provenge is awaiting the agency’s OK, and Merck KGaA’s Stimuvax is in trials for multiple myleoma, lung cancer, and breast cancer. But researchers hope that by making patients allergic to cancer early on, they can revolutionize the way the disease is treated.

UPMC researcher Olivera Finn is developing a vaccine to treat patients with advanced pancreatic cancer. While it’s shown some success, Finn believes the treatment will work best in those who haven’t yet developed the illness. So she’s testing it on subjects who have precancerous polyps, hoping that by administering the treatment early, disease progression can be halted. The idea is to make the body allergic to antigents, markers found on the surface of cancer cells. “If we immunize early on, the cells that become abnormal might actually be eliminated by a strong immune response,” says Finn. That immune response is most likely to work early in a disease, when the body’s immune system is still strong. Finn is several years away from reporting results.

In a different study being conducted by UPMC neurosurgeon Hideho Okada, researchers will test whether the immune system booster Hiltonol can slow or stop gliomas, a type of brain cancer. “Our goal is to educate the immune system so that it recognizes the cancer-specific antigens,” says Okada. Hiltonol, made by Seattle’s Oncovir, is being tested in 12 cancer vaccine trials. It sends a warning signal to the patient’s immune system telling it to attack the cancer.

Part of the challenge of testing preventative vaccines in people with early-stage cancer is time; patients would have to be followed for years for researchers to determine if early treatment was effective. And that’s enormously expensive. “It’s much easier to do that after you’ve got a revenue-generating product,” says Robert Kirkman, president of Oncothyreon, which originally developed Stimuvax. That’s why developers choose to treat late-stage diseases first

GoogleNews.com, Pittsburgh Post Gazette(PA), April 8, 2010  —  One of the persistent frustrations in cancer treatment has been the way that tumors can evade our immune systems as they grow and multiply inside our bodies.

Even though cancer cells have special surface markers, known as antigens, the body often doesn’t seem to be able to mount a full-fledged attack against the tumors, and the longer they last, the more they seem to suppress the immune response.

Yet it doesn’t have to be that way, says a dedicated band of scientists in universities and companies around the globe. In fact, they say, we may be on the verge of being able to vaccinate people against cancer in the same way we do with infectious diseases.

“I think we really are on the cusp of a revolution in cancer immunology,” said Andres Salazar, CEO of Oncovir, a Washington, D.C., company that makes an immune system booster for cancer vaccines. “We hope to make patients allergic to their cancers.”

The first commercial cancer vaccine out of the gate is likely to be sipuleucel-T, a vaccine against advanced prostate cancer being made by Dendreon Corp. of Seattle, Wash.

Not far behind in the pipeline is Stimuvax, a vaccine being made by Merck in Germany that targets a cancer marker known as MUC1, which is present in many different tumors.

That is the same target that UPMC researcher Olivera Finn has developed her own vaccine against.

Dr. Finn’s vaccine, which has been in development for several years, has already shown limited success in advanced pancreatic cancer patients.

But because she believes these vaccines will work best in people who do not yet have cancer, she and UPMC researcher Robert Schoen are testing the vaccine now in patients who have precancerous polyps in their colons, to see if it prevents the onset of colorectal cancer.

While she is still a couple years away from being able to report results, Dr. Finn knows the vaccine has created a strong immune response in the patients and has had few side effects.

The hope? “If we immunize early on, the cells that become abnormal might actually be eliminated by a strong immune response,” she said.

James Gulley, a leading vaccine researcher at the National Cancer Institute, agrees with that approach. He said there is growing evidence that the immune system doesn’t work as well against cancers that are more advanced, which “leads me to believe the best time to try vaccines thus might be before the tumor gets too large.”

That is also the goal of a new cancer vaccine trial being started here for patients with gliomas, a type of brain cancer.

That experiment, being run by UPMC neurosurgeon Hideho Okada, will administer the first vaccine ever developed for low-grade gliomas, which includes an immune system booster called Hiltonol.

These cancers are especially insidious, Dr. Okada said, because they often grow slowly for several years and the patients look and feel healthy. Then suddenly, they convert into an aggressive form of brain cancer that kills the patients.

“A low-grade tumor is not a benign tumor,” he said. “Unfortunately, a diagnosis with a low-grade glioma today is still a death sentence” — something he hopes the new vaccine can reverse.

The trial will be small to start with, involving 18 patients with new cancers and nine with recurrent tumors.

“We believe that immunotherapy could be long-lasting,” Dr. Okada said. “The actual drug doesn’t have to be present in the system, unlike chemotherapy, and the slow-growing nature of these gliomas gives us sufficient time to vaccinate and revaccinate patients.

“Our goal is to educate the immune system so that it recognizes the cancer-specific antigens.”

A key part of that will be the Hiltonol booster made by Dr. Salazar’s company.

The substance, named for co-inventor Hilton Levy, mimics the DNA of a virus, and seems to deliver a “warning signal” that fires up the immune system, Dr. Salazar said. It is being used now in about 12 different cancer vaccine trials, he said, including Dr. Okada’s.

Hiltonol is made of double-stranded DNA, “which doesn’t normally occur in mammalian cells,” he said, “but is a product of viral replication, so when mammalian cells see it, they say, “There’s a difference here. ”

Besides monitoring the patients who had colon polyps, Dr. Finn has also reported encouraging results with her vaccine in specially bred mice.

The mice have human genes that make them prone to get inflammatory bowel disease, which is a known risk factor for colorectal cancer. In fact, if they are left untreated, she said, about 80 percent of the mice will go on to get cancer.

When her team administered the MUC1 vaccine to the mice, though, not only did far fewer of them get inflammatory bowel disease, but almost none of them went on to get cancer.

The encouraging results of MUC1 vaccines aren’t confined to animals.

The version that is now being tested by Merck showed a 17-month survival advantage for advanced lung cancer patients who got the vaccine vs. those who didn’t in an earlier trial.

While the current testing has been suspended temporarily because one patient got encephalitis, the man whose company invented the vaccine is encouraged by the progress it has made.

Robert Kirkman, president of Oncothyreon, the Seattle, Wash., company that developed the vaccine, said he understands the logic of testing cancer vaccines on patients who aren’t as sick, but said that presents a financial challenge.

If vaccines were to be tested on a large group of patients with earlier stage cancer, it could mean following them for up to 10 years to see if the therapy was effective, and that would be enormously expensive.

If his company’s vaccine, Stimuvax, demonstrates a relative survival benefit for patients with later-stage cancers and can then be approved as a commercial product, he said, “it’s likely the work will then be done to show it works in earlier-stage disease, but it’s much easier to do that after you’ve got a revenue-generating product.”

The National Cancer Institute’s Dr. Gulley said he thinks there may be a middle ground between what is “biologically plausible and financially feasible” for testing cancer vaccines on human patients.

There is evidence that cancer vaccines take longer to show beneficial results than other kinds of therapies, he said, partly because the immune system needs time to gear up to fight the tumor.

In doing human trials of vaccines, he said, “if I were to err on one side or the other, I’d err on the side of what’s biologically plausible.” Too often in cancer treatment, “everyone’s looking for the big payoff with little effort, and that’s exactly the wrong thing to do.”

One other possible benefit of vaccines: They may make it possible for some people to live with their cancers for many years, even if the malignancies aren’t completely wiped out.

With Dr. Okada’s brain tumor patients, for instance, it would be a major advance if a vaccine could just stop their tumors from becoming aggressive and life-threatening.

Even with the addition of newer forms of chemotherapy in recent years, doctors who treat gliomas have only been able to extend average life spans by about three months over the past couple of decades.

“So if I could even make brain cancer a chronic disease like hypertension or diabetes,” he said, “I would be ecstatic.”

A cancer vaccine carried into the body on a carefully engineered, fingernail-sized implant is the first to successfully eliminate tumors in mammals, scientists reported in the journal Science Translational Medicine.
 

New approach reprograms the mammalian immune system to attack tumors body-wide

Contact: Steve Bradt
617-496-8070
Harvard University, CAMBRIDGE, Mass.  –  A cancer vaccine carried into the body on a carefully engineered, fingernail-sized implant is the first to successfully eliminate tumors in mammals, scientists report this week in the journal Science Translational Medicine.

The new approach, pioneered by bioengineers and immunologists at Harvard University, uses plastic disks impregnated with tumor-specific antigens and implanted under the skin to reprogram the mammalian immune system to attack tumors. The new paper describes the use of such implants to eradicate melanoma tumors in mice.

“This work shows the power of applying engineering approaches to immunology,” says David J. Mooney, the Robert P. Pinkas Family Professor of Bioengineering in Harvard’s School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering. “By marrying engineering and immunology through this collaboration with Glenn Dranoff at the Dana-Farber Cancer Institute, we’ve taken a major step toward the design of effective cancer vaccines.”

Most cancer cells easily skirt the immune system, which operates by recognizing and attacking invaders from outside the body. The approach developed by Mooney’s group redirects the immune system to target tumors, and appears both more effective and less cumbersome than other cancer vaccines currently in clinical trials.

Conventional cancer vaccinations remove immune cells from the body, reprogram them to attack malignant tissues, and return them to the body. However, more than 90 percent of reinjected cells have died before having any effect in experiments.

The slender implants developed by Mooney’s group are 8.5 millimeters in diameter and made of an FDA-approved biodegradable polymer. Ninety percent air, the disks are highly permeable to immune cells and release cytokines, powerful recruiters of immune-system messengers called dendritic cells.

These cells enter an implant’s pores, where they are exposed to antigens specific to the type of tumor being targeted. The dendritic cells then report to nearby lymph nodes, where they direct the immune system’s T cells to hunt down and kill tumor cells.

“Inserted anywhere under the skin — much like the implantable contraceptives that can be placed in a woman’s arm — the implants activate an immune response that destroys tumor cells,” Mooney says.

The technique may have powerful advantages over surgery and chemotherapy, and may also be useful in combination with existing therapies. It only targets tumor cells, avoiding collateral damage elsewhere in the body. And, much as an immune response to a bacterium or virus generates long-term resistance, researchers anticipate cancer vaccines will generate permanent and body-wide resistance against cancerous cells, providing durable protection against relapse.

Mooney says the new approach’s strength lies in its ability to simultaneously regulate the two arms of the human immune system: one that destroys foreign material and one that protects tissue native to the human body. The implant-based vaccine recruits several types of dendritic cells that direct destructive immune responses, creating an especially potent anti-tumor response.

“This approach is able to simultaneously upregulate the destructive immune response to the tumor while downregulating the arm of the immune system that leads to tolerance,” Mooney says. “In cancer, this latter arm is typically a limiting feature of immunotherapies, since it can extinguish vaccine activity and afford tumors a degree of protection.”

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Mooney’s co-authors are Omar A. Ali of Harvard’s School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering and InCytu, Inc.; Dwaine Emerich of InCytu, Inc.; and Glenn Dranoff of Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School. Their work was supported by the National Institutes of Health, Harvard University, and InCytu, Inc.
Read more: http://www.fiercebiotech.com/press-releases/implant-based-cancer-vaccine-first-eliminate-tumors-mice#ixzz0kWVvbbrf