Radioactive Bacteria Designed to Treat Metastatic Pancreatic Cancer

Scientists have developed a pancreatic cancer therapy that uses Listeria bacteria to selectively infect tumor cells and deliver radioisotopes into them. The investigational treatment was shown to drastically decrease the number of metastases in a mouse model of highly aggressive pancreatic cancer without injuring normal tissue.

The study’s findings were published April 22, 2013, in the online edition of the Proceedings of the National Academy of Sciences of the United States of America (PNAS). “We’re encouraged that we’ve been able to achieve a 90% reduction in metastases in our first round of experiments,” said cosenior author Claudia Gravekamp, PhD, associate professor of microbiology and immunology at Albert Einstein College of Medicine of Yeshiva University (Bronx, NY, USA), who studies new approaches to treating metastatic cancer. “With further improvements, our approach has the potential to start a new era in the treatment of metastatic pancreatic cancer.”

Scientists, a while ago, observed that an attenuated form of Listeria monocytogenes could infect cancer cells, but not normal cells. In a 2009 study, Dr. Gravekamp discovered why—the tumor microenvironment inhibits the body’s immune response, allowing Listeria to survive inside the tumors. By contrast, the weakened bacteria are rapidly eliminated in normal tissues.

Scientists later demonstrated that Listeria could be exploited to convey an anticancer drug to tumor cells in laboratory cultures, but this strategy was never assessed in an animal model. These findings encouraged Dr. Gravekamp to examine Listeria-tumor interactions and how Listeria could be used to attack cancer cells.

The concept of attaching radioisotopes (typically utilized in cancer therapy) to Listeria was suggested by Ekaterina Dadachova, PhD, professor of radiology and of microbiology and immunology at Einstein and the study’s cosenior author. Dr. Dadachova, is a pioneer in developing radioimmunotherapies, i.e., patented treatments in which radioisotopes are attached to antibodies to selectively target cells including cancer cells, microbes or cells infected with HIV. When the antibodies bind to antigens that are unique to the cells being targeted, the radioisotopes emit radiation that selectively kills the cells.

Working together, Drs. Gravekamp and Dadachova coupled the radioactive isotope rhenium to the weakened Listeria bacteria. “We chose rhenium because it emits beta particles, which are very effective in treating cancer,” said Dr. Dadachova. “Also, rhenium has a half-life of 17 hours, so it is cleared from the body relatively quickly, minimizing damage to healthy tissue.”

Mice with metastatic pancreatic cancer were given intra-abdominal injections of the radioactive Listeria once a day for seven days, followed by a seven-day “rest” period and four additional daily injections of the radioactive bacteria. After 21 days, the scientists counted the number of metastases in the mice. The treatment had decreases the metastases by 90% compared with untreated controls. Furthermore, the radioactive Listeria had concentrated in metastases and to a lesser extent in primary tumors but not in healthy tissues, and the treated mice did not appear to suffer any ill effects.

The treatment may have the possibilities for treating an even higher percentage of metastases. “We stopped the experiment at 21 days because that’s when the control mice start dying,” said Dr. Dadachova. “Our next step is to assess whether the treatment affects the animals' survival.”

“At this point, we can say that we have a therapy that is very effective for reducing metastasis in mice,” Dr. Gravekamp noted. “Our goal is to clear 100% of the metastases, because every cancer cell that stays behind can potentially form new tumors.”

The researchers expect the treatment could be enhanced by using higher doses of radiation, modifying the treatment schedule, or by adding more anticancer agents onto the bacteria. Einstein has filed a patent application related to this research that is currently available for licensing to partners interested in further developing and commercializing this technology.

Related Links:
Albert Einstein College of Medicine of Yeshiva University