Cancer Immunotherapy: Training dendritic cells

Anti-cancer implant

Alexey Levin, Voice of AmericaHarvard researchers have successfully tested in the laboratory a very promising option for targeting immune cells to destroy malignant tumors.

With the help of this technique, they managed to save almost all the mice doomed to imminent death from malignant melanoma. These experiments are described in an article by Professor of bioengineering Technologies David Mooney and co-authors, which appeared in the February issue of the journal Nature Materials (Omar A. Ali et al., Infection-mimicking materials to program dendritic cells in situ).

Cancer immunotherapy is a targeted mobilization of the immune system to fight malignant tumors. The term itself has appeared relatively recently, but actually it has a very old idea behind it. Even at the end of the 18th century, doctors noticed that in some cancer patients, tumors decrease in size or even completely disappear after an infectious disease. Later, such classics of medicine of the 19th century as Louis Pasteur and Robert Koch drew attention to this. In 1890, a New York doctor, William Coley, even began injecting live and killed bacteria and extracts of bacterial cultures to cancer patients, and such treatment helped some people. However, microbial infection rarely led to success and gave too many complications, so other doctors did not support this innovation.

Much later, scientists came to the conclusion that infection with bacteria causes the body to produce a biologically active substance that either kills tumor cells or reduces the rate of their division. In the mid-70s of the last century, it was proved that a specific protein acts in this role, which was called a tumor necrosis factor. It is synthesized by some immune cells, in particular, macrophages. It follows from this that Kolya's vaccines actually tuned the immune system to eliminate tumor foci, so that he deservedly entered the history of medicine as the discoverer of cancer immunotherapy.

In recent years, oncologists have tried many experimental methods of antitumor immunotherapy. One of them is based on the use of dendritic cells, one of the varieties of cells of the immune system. Dendritic cells by themselves do not destroy cancerous growths, their task is different. They recognize specific proteins-antigens located on the surface of cancer cells, and then activate killer lymphocytes that directly attack the tumor. However, under normal conditions they do not do it very effectively. The task of immunotherapy is to make dendritic cells react strongly and precisely to the form of cancer that the patient suffers from. The question arises, how best to do this?

Usually, in such cases, oncologists act according to the following scheme. Dendritic cells are isolated from the blood of a cancer patient and then, already "in vitro", are forced to contact tumor antigens. At the same time, chemical stimulants are injected there, which help cells recognize tumor proteins. After that, the trained dendrites are reintroduced to the same patient.

Unfortunately, so far the practical value of this method has turned out to be low. He proved himself well in animal experiments, but did not benefit patients of ocological clinics. The fact is that human dendritic cells are very unstable and therefore mostly die during transplantation.

Professor Mooney and his colleagues have found a way to overcome this difficulty. They decided to train dendritic cells not on the laboratory table, but directly in the patient's body. For this purpose, a special implant made of a biodegradable porous polymer is used. He sits down under the skin next to the tumor and begins to work on its destruction.

That's how it happens. A polymer disk designed for implantation with a diameter of less than a centimeter is loaded with a specially designed biological filling that fills its numerous pores. After planting, it releases signaling molecules that attract dendritic cells to it. When these cells migrate into tiny holes on the surface of the implant, they meet tumor antigens there and learn to recognize them. To make this task easier for them, the experimenters inject fragments of bacterial DNA into the same pores, which significantly enhance the anti-cancer reaction of dendritic cells.

In a sense, the old scheme of William Kohli works here, only in a completely different version. Well-trained dendritic cells leave the implant, migrate to the lymph nodes of animals and activate T-lymphocytes there, which zealously attack tumor foci. In this way, 90% of the mice used in these experiments were cured of melanoma. In vitro training of dendritic cells, this indicator does not rise above 60%.

Professor Mooney and his colleagues believe that their technology has a great future. They believe that not only dendrites, but also other immune cells can be trained in polymer implants. They can be trained to fight not only tumors, but also autoimmune diseases, such as type I diabetes and rheumatoid arthritis. In general, Harvard scientists have extensive plans.

In the near future, the Muni group intends to still engage in cancer immunotherapy. Now Harvard scientists will have to test how anti-cancer implants will work when transplanted to larger animals. In addition, it is necessary to find out to what extent they prevent the development of metastases. If these experiments do not bring disappointments, it will be possible to plan clinical trials of a new therapy.

Portal "Eternal youth" www.vechnayamolodost.ru29.01.2009