Measles Virus Retargeted at Cancer Cells in Mice

An international team of researchers has re-engineered a robust strain of the measles virus to find and attack only cancer cells in a proof-of-concept study in mice published in the February 2005 issue of Nature Biotechnology. While development of clinical therapies is still years away, the new Six-his[tidine] Tagging and Retargeting (STAR) system opens the door to a new class of "retargeted viruses from other virus families," reported study leader Dr. Stephen J. Russell of the Mayo Clinic.

Viruses survive by penetrating a cell and commandeering its ability to reproduce. About 5 years ago, scientists discovered that the common measles virus was "oncolytic," with the ability to preferentially attack cancer cells. They began to search for ways to neutralize the measles virus' indiscriminate assault on healthy cells while retaining its potency against cancer - an approach known as oncolytic virotherapy.

Dr. Russell and his colleagues created the STAR system by first disabling the measles virus from attacking normal cellular targets. They then re-engineered the virus to effectively fuse to receptors on the cell membranes of new targets: a trans-membrane molecule (CD38) and a receptor (EGFR) found at abnormally high levels on the surface of many cancer cells. Finally, they discovered a "molecular tag" that permits the new virus to be propagated in large quantities on universal substrate cells. The STAR system produces "very clean, very clear targeting," said Dr. Russell. "We can take our pick as to what new receptor we target and send the virus after it."

Managed Care Growth Doesn't Sap Fee-for-Service Care Quality

The quality of cancer care provided by the fee-for-service sector in a given region does not appear to be negatively affected by an increased managed care presence in the same area, a new NCI-funded study concludes. The authors note that the study provides some assurance that fee-for-service providers are not shortchanging patients by offering less - or at least less expensive - care in an effort to contain costs and compete with managed care providers. Fears that such a "spillover effect" might be occurring, lead author Dr. Nancy L. Keating and colleagues from Harvard Medical School wrote, have grown as managed care has continued to be a formidable presence in many parts of the country.

Published in the February 16 Journal of the National Cancer Institute, the study used data from NCI's Surveillance, Epidemiology, and End Results (SEER) program and Medicare on more than 89,000 patients who had been diagnosed with breast or colorectal cancer between 1993 and 1999. They focused their review on several indicators of quality care, including use of surveillance mammography after breast cancer diagnosis, use of radiation therapy after breast-conserving surgery, and use of adjuvant chemotherapy in patients with stage III colorectal cancer.

The only truly marked effect of expanded managed care penetration on fee-for-service providers was an increased rate of carcinoembryonic antigen testing for patients with colorectal cancer, which increased significantly as managed care market share grew.

"Performance on most indicators of quality was relatively poor overall," the authors wrote. "Our observed rates were consistent with those reported in other studies, suggesting that substantial improvements in quality remain possible."

Protein Test Could Detect Bladder Cancer Earlier

Researchers have found that testing for the nuclear mitotic apparatus protein (NMP22) - which is released into the urine during cell death and often elevated in the presence of malignancy - could become an important tool for diagnosing patients who are being screened for bladder cancer.

In a study published in the February 16 Journal of the American Medical Association, a team led by Dr. H. Barton Grossman from the University of Texas M.D. Anderson Cancer Center found that the NMP22 protein marker successfully detected tumors 3.5 times more effectively than did standard cytology tests.

The study enrolled 1,331 patients with bladder cancer risk factors or symptoms at 22 sites. Overall, 79 cases of bladder cancer were detected in the study group. Participants were screened for indications of bladder cancer using either the new NMP22 protein test or the current standard cytology analysis. The cytology diagnostic tool has very high specificity but is "offset by low sensitivity, ambiguous test results, expense, and time lag to obtain reports," said the authors.

If further studies confirm the findings of the NMP22 assay, it could help diagnose bladder cancer earlier, before the disease has spread, the researchers concluded. NMP22 testing could become an important complement to cystoscopic imaging for detecting bladder cancer. Results of the noninvasive test are available during the same patient visit as the screening.

The NMP22 protein was detected by a device that is intended to be used at point-of-care in physicians' offices and clinics. The NMP22® BladderChek® Test device is made by Matritech, Inc., of Newton, Mass., which provided funding for the study.

Researchers Develop Nanoprobes to Visualize Tumors
Inside the Body

Scientists at the University of Pennsylvania and the University of Minnesota have designed organic nanoprobes that enable them to use infrared light to visualize tumors deep below the skin surface of rats. Their findings, which demonstrate a novel optical imaging approach through "soft matter," appear in the February 22 edition of Proceedings of the National Academy of Sciences.

The probes were created using synthetic polymers that aggregate into spherical vesicles, or polymersomes, in the presence of water. The researchers then interspersed fluorescent molecules called porphyrins throughout the vesicle surface, creating tiny organic spheres that "light up" when struck by infrared light. Because infrared light has a longer wavelength than visible light, the researchers could see deeper into tissue.

They injected the vesicles into a glioma tumor 1 centimeter below the skin in a rat and saw a highly localized fluorescence. The polymersomes also proved to be stable; when placed in blood plasma heated to human body temperature, the vesicles maintained a constant fluorescence for a week.

The researchers believe polymersome vesicles may be well-suited for deep-tissue imaging. They can be made biodegradable, posing little risk of build-up in the bloodstream. Therapeutic agents can be dissolved in the aqueous center, allowing for drug delivery to the tumors while they are imaged. "Another feature that makes polymersomes useful is that they self-assemble," added author Daniel Hammer. "Simply mixing together all the component parts gives rise to these functional cell-like vesicles."

Symposium on Cancer Screening and Mortality at AAAS At the American Academy for the Advancement of Science (AAAS) annual meeting, held in Washington, D.C. February 17-21, a panel of experts from cancer research institutions around the country discussed the successes and shortcomings of cancer screening. Dr. Barnett Kramer, who heads NIH's Office of Disease Prevention and is editor-in-chief of the Journal of the National Cancer Institute, began the session on February 20 by pointing out that cancer screening often involves a "clash between science and intuition." Explaining the different ways that screening studies can incur bias and mislead people to believe that the results are significant when in fact they may not be, he presented data showing that screening has not reduced mortality in some cancers. "Unless we have a net benefit" in screening cancer patients, he said, "we could be in the position of incurring higher cost with net harm." Dr. Diane Solomon of NCI's Division of Cancer Prevention talked about cervical cancer screening, observing that it "is the poster child of what cancer screening can achieve." She discussed HPV infection, its incidence among younger and older women, and how this has influenced screening recommendations demographically. "Cervical cancer screening is a misnomer," she said. "We're not detecting cancers - when it's too late - we're detecting precancers." Other speakers that morning included Dr. Ian Thompson of the University of Texas Health Science Center, Dr. Sandra Lee of the Dana-Farber Cancer Institute, Dr. Timothy Rebbeck of the University of Pennsylvania School of Medicine, and Beth Peshkin of Georgetown University. Abstracts of their talks can be accessed at: http://php.aaas.org/meetings/MPE_01.php.