23 April 2013

A new method of delivering radioisotopes to metastases

Bacteria infected cancer

Nadezhda Markina, <url>American scientists have invented a very unusual way to treat cancer: they have attracted Listeria bacteria as allies that selectively infect cancer cells.

The idea is to use them as couriers to deliver radioisotopes. And the latter destroy malignant cells by emitting radioactive particles.

The method proved to be particularly effective against metastases. In the experiment, the researchers managed, with the help of bacteria, to almost completely rid laboratory mice of metastases of exceptionally aggressive pancreatic cancer.

Pancreatic cancer is one of the most dangerous types of cancers, it ranks fourth in mortality, the share of five-year survival is only 4%. According to forecasts of the National Cancer Institute, more than 45 thousand such diagnoses will be made in the USA this year, and more than 38 thousand people will die from pancreatic cancer. There has not been any significant improvement in his treatment over the past 25 years.

The problem is that this cancer is rarely detected at an early stage, when it is limited to the pancreas. In most cases, cancer is diagnosed after the tumor has metastasized. After that, symptoms appear – jaundice, pain, weight loss and weakness. At this stage, cancer cannot be cured, and the task of doctors is only to improve the quality of life of the patient.

Specialists from the Albert Einstein College of Medicine at Yeshiva University, New York, discovered several years ago that weakened Listeria monocytogenes bacteria can selectively infect cancer cells without infecting normal cells. In 2009, Claudia Gravecamp, associate professor of microbiology and immunology, found the cause. The tumor microenvironment suppresses the immune response, and this is what allows bacteria to survive in cancer cells.

Listeria monocytogenes and other listeria enter the body through the gastrointestinal tract, but usually in humans the bacteria die after 3-5 days due to the activity of the immune system. Scientists have tried to use listeria as a vehicle, loading them with anti-cancer drugs. They have tested the effectiveness of such transport on cell cultures, but have not yet conducted experiments on animals.

The idea to load bacteria with radioisotopes belongs to Ekaterina Dadachova, professor of radiology at Einstein College, a specialist in radioimmunotherapy. This is a method of targeted cancer therapy in which radioisotopes are attached to antibody proteins that carry them directly to the targets – malignant cells. On the surface of these cells, antibodies combine with antigens, and radioisotopes emit deadly rays that kill these cells. In a joint work, Gravecamp and Dadachova attached a radioisotope of rhenium (188Re) not to an antibody, but to weakened Listeria bacteria. "We chose rhenium because this isotope releases beta particles that are particularly effective in destroying cancer cells," Dadachova emphasizes. "in addition, rhenium has a half–life of 17 hours, so it is relatively quickly eliminated from the body, minimally damaging healthy tissues." The authors published the results of their work in the journal Proceedings of the National Academy of Sciences (Quispe-Tintaya et al., Nontoxic radioactive Listeria at is a highly effective therapy against metastatic pancreatic cancer).

Experimental mice with vaccinated pancreatic cancer, which has already spread through the body in the form of metastases to the liver, spleen, kidneys and lymph nodes, were injected with a suspension of weakened bacteria with a load of rhenium directly into the stomach. The introduction was repeated daily for seven days, then they took a seven-day break and conducted a repeat course. The study of the tissue showed that listeria was concentrated to a greater extent in metastases and to a lesser extent in the primary tumor. In healthy tissue, there were no bacteria at all. After 21 days, when the mice in the control group began to die from cancer, the researchers calculated the number of metastases in both groups. They were very surprised that 90% of metastases disappeared in animals treated with radioactive bacteria compared to the control group.

Radioactive radiation damages the actively dividing cells of a malignant tumor much more. In this case, it had the greatest effect on metastases.

"We are very encouraged that we managed to achieve a 90% disappearance of metastases already in the first experiment," says Claudia Gravecamp. "With the improvement of our approach, it can open a new era in the treatment of metastatic pancreatic cancer."

Now the authors are patenting their method and are going to develop it. Scientists set themselves the task of achieving 100% disappearance of metastases. They believe that the method has ways to improve, which consist in increasing the dose of radioisotopes or adding chemical anticancer agents to the bacterial "package".

Portal "Eternal youth" http://vechnayamolodost.ru23.04.2013

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