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 Nov. 27 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 it 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, 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, which 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 bacteriolytic 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, 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.