SemiOT:New Bacteria Target Cancers in Mice
hopkinscancercenter.org
NOVEMBER 26, 2001
Media Contact: Vanessa Wasta
wastava@jhmi.edu
Scientists from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins have created bacteria that selectively target large advanced tumors in mice. Results of their experiments are reported in the November 27, 2001 issue of the Proceedings of the National Academy of Sciences.
The scientists found a way to exploit a special germ’s taste for oxygen-starved environments and direct them to target pockets of dead and dying cells within large tumors. These advanced tumors generally have areas of poor blood circulation and thus little oxygen. The lack of oxygen renders them relatively resistant to conventional chemotherapy and radiation but open to bacteria that can grow without oxygen.
“The idea is to selectively attack these tumors from inside with the bacteria and from the outside with chemotherapy,” says Bert Vogelstein, M.D ., Clayton Professor of Oncology and Investigator, Howard Hughes Medical Institute.
The scientists systematically screened numerous bacterial species to find one that would thrive in an oxygen-poor environment and, at the same time, destroy surrounding tumor cells. They settled on one spore-forming bacterial species, called Clostridium novyi (C.novyi).(photo is @ hopkinscancercenter.org C.novyi is normally found in soil and dust and contains a toxin that can cause lethal side effects in animals. They genetically modified the bacteria to remove the toxin gene to make them harmless to normal animals. Then, they injected spores of these bacteria and conventional chemotherapeutic agents into mice with large tumors composed of transplanted human colon cancer cells.
The results achieved with this strategy, called COBALT for combination bacteriol ytic therapy were dramatic. More than half of the tumors treated, including very large tumors, were completely destroyed within 24 hours. The tumors decomposed and turned into blackened scars, while the surrounding healthy tissues remained intact. The tumor scars then gradually disappeared over the next two weeks, leaving healthy tissue behind.
Clinical trials are not planned at this time as it will take several years to determine which chemotherapy agents make the best combinations and to develop strategies to avoid the toxicity associated with rapid destruction of large tumor masses. “We hope that this research will add a new dimension to cancer treatment, but realize that the way tumors respond to treatment in mice can be different than in humans,” says Kenneth Kinzler, Ph.D ., professor of oncology.
Funding for this research was provided by the Miracle Foundation, the National Colorectal Cancer Research Alliance, the Clayton Fund, and the National Institutes of Health.
In addition to Vogelstein and Kinzler, participants of this research include Long H. Dang, Chetan Bettegowda, and David L. Huso from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
The picture below shows the new bacteria (green) destroying tumor cells (red) in the middle of a large cancer in mice. The bacteria were injected intraveneously 12 hours before this picture was taken.
Bert Vogelstein, M.D.
Clayton Professor of Oncology
Investigator, Howard Hughes Medical Institute
Johns Hopkins Oncology Center
Bert Vogelstein, M.D., is a leading international expert and pioneer in the field of molecular genetics. His expertise in using the exquisitely sensitive tools of molecular biology has led to the discovery of a series of genetic mutations that cause the initiation and progression of colon cancer. Among his discoveries are the role of the p53 gene in cancer, now considered the most commonly mutated gene among all cancers; the APC gene, linked to familial adenomatous polyposis (FAP) and familial colon cancer (FCC); and several mismatch repair genes involved in the onset of hereditary non-polyposis colon cancer (HNPCC). Key papers on colon cancer published by Vogelstein over the last two decades have made him the most highly cited scientist in the world.
Kenneth W. Kinzler, Ph.D.
Professor of Oncology
Johns Hopkins Oncology Center
As co-director of the Johns Hopkins Oncology Center's Molecular Genetics Laboratory, Kenneth Kinzler, Ph.D., has played a pivotal role in uncovering a series of genetic alterations linked to the development and progression of colon cancer. He is among the most highly cited scientists in the world and is a leading expert on the APC gene and colon cancer. He gained international recognition for his development of a computerized system called SAGE (sequential analysis of gene expression) which provided the first reported comprehensive analysis of gene expression in cancer cells. This technology now allows researchers to study thousands of genes at the same time, measure their expression, and pinpoint differences between normal and tumor cells.
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Very interesting Rich. Thanks for the info. Looks like the people doing the research at JH are pretty well respected scientists. All approaches to curing cancer are on the table. Vion has the upper hand right now since they are already in clinical trials with their bacteria stuff (TAPET). vionpharm.com
Rich, quite sometime ago, I thought it was on this thread, you were expressing concern about possible toxicity issues with TAPET. Any update on your view of things now would be appreciated. Thanks.
Jim |
