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Record: 1 Title: Authors: Source: Document Type: Subject Terms: On the Twisting Trail of Cancer Vaccines. Tsao, Amy Carey, John BusinessWeek Online; 8/18/2003, pN.PAG, 0p Article *CANCER -- Treatment *RESEARCH *VACCINES *VACCINATION *THERAPEUTICS NAICS/Industry Codes923120 Administration of Public Health Programs Abstract: Discusses issues related to the progress in cancer vaccine research as of August 2003. Goal of cancer vaccine; Details of the new cancer treatments in development; Approaches of cancer-vaccine research. Full Text Word Count: 1280 Accession Number: Database: 10584675 Academic Search Premier

Full Text Database: Section: Technology THE BIOTECH BEAT

On the Twisting Trail of Cancer Vaccines

While success has eluded huge drug companies and small biotechs so far, scientists now have a better idea of what might work As cancer researcher Dr. Olivera Finn tells it, therapeutic cancer vaccines have a way of confounding scientists. "Once in a while, there's a response. Once in a while, we see stabilization. Once in a while, a patient lives longer than expected." After nearly 20 years of studying vaccines, Finn says her work is still about "doing everything you can imagine to eek out a little bit of success. That won't solve the cancer problem." Though progress is frustratingly slow, Finn, chief of immunology at the University of Pittsburgh School of Medicine and author of a recent review of cancer-vaccine research in Nature, still believes that cancer vaccines will become a reality. And she's not alone. Vaccines remain one of the most promising -- and daunting -- areas of cancer research. Even with all the advancements in other cancer treatments in recent years -- like Genentech's (DNA) and Idec's (IDPH) respective antibodies Herceptin and Rituxan and Novartis' targeted therapy Gleevec -- vaccines intrigue researchers. In theory, they should cause fewer side effects than traditional cancer drugs. The concept behind cancer vaccines differs from both traditional vaccines and cancer treatments. The 27/09/2011


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goal of a cancer vaccine, unlike prophylactic shots for ailments like flu, isn't to prevent disease but to trick the immune system, which has already missed the existing cancer cells, to attack them. Unlike traditional chemotherapy drugs, which kill cells unselectively, vaccines aim to help the body kill off cancer cells only. INCONCLUSIVE RESULTS. Some 13% of all new cancer treatments in development are therapeutic vaccines, according to pharmaceutical-industry consulting firm Decision Resources. Many heavyweights like Genzyme (GENZ) (through its Genzyme Molecular Oncology unit), Aventis Pasteur (AVE), and GlaxoSmithKline (GSK) have ongoing cancervaccine projects in early phases. The National Institutes of Health is funding several projects. And a dozen or more biotechs have vaccine at various stages of development, including Cell Genesys (CEGE), Genitope, and Therion Biologics. At least eight vaccines are now in late Phase 3 testing. But so far results from large trials have been discouraging. Two years ago, Corixa's Melacine vaccine didn't produce the harsh side effects of chemotherapy, but results were inconclusive, except in a subgroup of patients. This summer, Biomira's (BIOM) breast-cancer vaccine Theratope, which is being developed with Germany's Merck, had a similar result. Finn thinks the trials have been flawed. While informative, none to date, including trials she has been involved in, have merited the broad human testing that has been done, Finn contends. Smaller companies, often with modestly positive data at best, are often under pressure to initiate big trials to keep their investors interested. All of the failed studies then "look like a failure of our science," Finn says. DUAL PATHS. The best prospects among therapeutic cancer vaccines may ultimately be in earlier-stage research efforts -- projects that began as knowledge of how to construct viable vaccines and became more comprehensive. Vaccines like Melacine represent the best of an early generation of such therapies, says David Fanning, Corixia's chief operating officer, because they have "greater specificity and cleaner ability to test for immune response." Cancer-vaccine research falls mainly in two camps: antigen-specific and whole-cell. The first approach tries to increase recognition of antigens -- foreign substances that appear on intruding cells -- known to be related to certain cancers. Whole-cell vaccines are tailored to a patient's own tumor cells or a combination of other people's cancer cells. Test details vary -- in terms of the type of patients selected, how the vaccine is delivered (with a virus or a different method), what so-called adjuvant drug is used to prime the immune system to best respond to the vaccines and which specific antigens to go after. Though many companies are still testing them, whole-cell strategies are beginning to lose some luster while vaccines that target specific antigens seem to be garnering more champions. With whole-cell vaccines, it isn't clear which elements are having an effect on the cancer. "We have so much knowledge in precision molecules and understanding specificity, then we ignore it to get any kind of immune response," says Finn. 27/09/2011


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Mitchell Gold, chief executive of Dendreon agrees: "With [whole-cell] vaccines, it's a potpourri." At least two of the vaccines in late-stage testing are whole-cell: Cancervax's Canvaxin and Antigenics' Oncophage. RECOGNITION BOOSTER. An antigen-specific treatment with a shot at approval is Seattle-based Dendreon's Provenge, which targets a prostate-cancer antigen seen in 95% of men with that illness. Provenge also has the added ingredient of a sample of a patient's so-called dendritic cells, which boost the vaccine by alerting other immune system cells to recognize antigens and mount an immune response. Provenge is now in its second Phase 3 trial. In 2001, Dendreon reported, as had others before it, successful results in just a subset of patients. Fortunately, the subset represented some 75% of men with prostate cancer -- those with less aggressive tumors who were no longer responding to hormone treatments. Patients given Provenge saw their chances of surviving more than double and experienced a significant delay in disease-related pain, says Dendreon's Gold. "Others are promising, but I think the proof is in our data," he says. All the data from the second Phase 3 trial will be available sometime in 2005. "THAT'S A CLUE." Earlier-stage anitgen-specific projects at French drugmaker Aventis Pasteur are showing some promise. Dr. Neil Berinstein, assistant vice-president for clinical oncology and cancer program director, says the company has done four Phase 1 trials in colorectal-cancer patients. "We're eager to move as fast as possible on cancer vaccines," he says. Aventis is using the CEA antigen, commonly seen in colon-cancer cells, in a gene-therapy treatment. In response to the vaccine, the body is supposed to make the antigen, which is then supposed to stimulate the immune system to attack the antigen. "We've shown it's safe and that most patients have a CTL -- i.e. cyotoxic lymphocycte, or killer T-cell -response to CEA," says Berinstein. "And in some patients who failed chemo, we've seen a stabilization. That's a clue that something is happening." Berinstein, naturally, is bullish on the approach. "This will be a big growth area," he predicts. "Sometime in the next decade, almost every patient will receive a cancer vaccine." Not as the only therapy, he hastens to add, but as part of a combination regimen. Aventis-Pasteur is also doing trials in melanoma patients. "We've found that the vaccine is safe, and we get high levels of T-cell activation -- and some actual tumor response." NO ANIMAL TESTING. While cancer vaccines continue to intrigue many reasearchers, some companies are losing patience. Jean Stephenne, president of GlaxoSmithKline's vaccine unit, said recently: "We have reduced our effort in cancer vaccines. It's really a gamble." He says one key problem is that no animal models exist, so the only way of getting data is with human trials. Still, Glaxo is working with Corixa on development of 27/09/2011


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vaccines for breast and prostate cancer. Trial data will be available in 2006, says Stephenne. In the next two years, several companies will unveil results from late-stage trials for cancer vaccines, but if the Phase 3 disappointments of the past are any indication, a real product on the market could still be very far away. Nothing is for sure in drug research, and the field will likely test the patience of investors, the medical community, and cancer sufferers alike for many more years to come. ~~~~~~~~ By Amy Tsao and John Carey Copyright of BusinessWeek Online is the property of Bloomberg, L.P. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. 27/09/2011