Cancer Immunotherapy: a mini-review
The Achilles heel of cancer
A new drug for the treatment of breast cancer
included in the priority list by the US national regulator Anastasia Kuzkina, "Newspaper.
In this regard, the Department of Science "Newspapers.Ru" has prepared an overview of the most advanced modern methods of oncotherapy.
The pharmaceutical company Hoffmann-La Roche announced on its official website that the US Food and Drug Administration (FDA) has given the right of priority evaluation to the innovative drug T-DM1 (trastuzumab entanzine) developed in its laboratories for the treatment of aggressive breast cancer (FDA grants Roche's trastuzumab emtansine (T-DM1) Priority Review for HER2-positive metastatic breast cancer). This medicine is among the fundamentally new means of treating malignant tumors.
The FDA has recognized the social significance of the new drug: the right of Priority Review means that the procedure required for approval of a new drug by a national regulator will take a minimum time (6 months instead of the usual 10-18 months).
T-DM1 prolongs the life of breast cancer patients for 6 months longer compared to other treatments and does not cause toxic side effects, such as hair loss.
There are three main methods of treating tumors that came to us from the twentieth century and have not yet lost relevance: surgical removal, chemotherapy and radiation therapy. All of them are not without serious drawbacks. Chemotherapy is based on intravenous administration of drugs that cause the death of not only tumor cells, but also cells of those tissues of the body that are constantly being updated. Therefore, patients experience serious adverse events: hair loss, diseases of the gastrointestinal tract and hematopoietic system. Radiation therapy damages the tissues surrounding the tumor: depending on the irradiated area, the patient may experience diarrhea, baldness, infertility, joint problems, or even develop a new tumor. With surgical removal of a tumor, it is not always possible to destroy all tumor cells. Even if only one remains, it will give rise to a new tumor.
One of the most promising areas in the treatment of tumors is biological therapy, or immunotherapy. Such treatment does not cause the death of tumor cells directly, but helps the human immune system to recognize and destroy the tumor itself. Biological therapy has a selective effect on the subtle mechanisms underlying the tumor process, and is therefore safer than other methods of treatment.
Some biotherapeutic drugs have already entered clinical use (at the moment, the FDA has approved 12 monoclonal antibodies and 1 vaccine), but this is only the tip of the iceberg: a huge number of studies are currently underway to find and test new biological drugs. In the USA alone, according to the National Cancer Institute, there are 277 clinical trials of various antitumor vaccines and 1,600 studies on monoclonal antibodies.
In order to understand the principle of action of these drugs, it is necessary to study the mechanism of occurrence of malignant tumors. A cancerous tumor develops from just one cell, which ceases to perform its normal functions and begins to divide rapidly and uncontrollably. The reason for this behavior is a mutation, damage to the structure of the gene. Mutations occur if a cell makes a mistake when doubling its genetic material before dividing or as a result of exposure to adverse factors, so-called carcinogens (for example, tobacco smoke or ultraviolet rays).
It is not easy for an ordinary cell to turn into a tumor cell. As a rule, damage to the genetic material either triggers a special system that corrects the error, or leads to the self-destruction of the defective cell. The function of the immune system is to maintain the constancy of the cellular composition of the body. The cells of the immune system "remember" the gene structure of all the inhabitants of their body, and if they come across a "nezakomets", be it a bacterium, a virus or their own defective cell that could give rise to a tumor, then it is destroyed.
The immune system does not always cope with this task. The fact is that tumor cells do not have many differences from normal cells, they are like spies in a number of normal cells of the body – it is not always possible to calculate their immunity. In addition, tumor cells can defend themselves by suppressing the patient's immune response.
To defeat the tumor, scientists are trying to influence various links of the tumor process and the immune response. In recent years, many targets have been found, the impact on which should help the patient's body cope with cancer. The so-called monoclonal antibodies are able to attack some of these targets.
Monoclonal antibodies are ready–made "protectors", artificially created analogues of human antibodies - protective substances produced by cells of the immune system. They bind to specific targets on tumor cells, stop its growth, initiate tumor self-destruction, or stimulate an immune response. For example, bevacizumab, used to treat colorectal cancer, lung cancer and glioblastoma, blocks the growth of blood vessels in tumor tissue. Without blood vessels, the tumor does not receive enough oxygen and nutrients, and its growth stops.
Other antibodies bind to certain receptors on the surface of tumor cells, thus "telling" the immune system where to attack. Similar drugs have already been developed for the treatment of non-Hodgkin's lymphoma and some types of leukemia.
It is also possible to stimulate the immune system by turning off the "brakes" – various cellular mechanisms that regulate the immune response. This is how ipilimumab works – a new drug for the treatment of melanoma. Ipilimumab blocks the CTLA-4 receptor, which is a kind of "switch" of T-lymphocytes. Its blocking leads to the development of a full and strong immune response that destroys the tumor.
Another drug, MK–3475, acts on another link of the immune response - the PD–1 B–lymphocyte receptor (programmed cell death - a receptor for programmed cell death), which also leads to the awakening of the immune system.
Monoclonal antibodies can also be used as carriers of chemo- and radiotherapy, since an antibody bound to a molecule of a chemotherapy drug or a radioactive substance is able to selectively bind specifically to tumor cells. Thus, the effectiveness of therapy increases and the adverse effects of toxic substances on healthy cells are reduced. An example of such a drug is the trastuzumab-DM1 described above – a combination of an antibody and a chemotherapy drug.
Another new way to fight cancer is antitumor vaccines. Vaccines, unlike monoclonal antibodies, act on the very first link of the immune response, "teaching" the immune system itself to recognize the threat and destroy the tumor. Also, unlike conventional preventive vaccines, such as influenza or hepatitis B vaccines, antitumor vaccines do not serve to prevent the disease, but to treat an already sick person. However, like the vaccines we are used to, they contain a "piece" of a foreign agent (in this case, a tumor cell) – an antigen that can only be found in this tumor.
For example, the CDX-110 vaccine contains a protein product of a mutated gene that is produced only by cells of a single tumor – glioblastoma. The immune system activated by the vaccine selectively destroys the cells of this tumor.
Other vaccines contain DNA or RNA molecules – "instructions" for the production of substances capable of destroying the tumor. The molecules are transferred by means of a harmless virus that penetrates into cells, cells read information from DNA or RNA and themselves produce enough antigen to activate the immune system.
Finding the right antigens is a very difficult task. For example, in two patients with lung cancer, different mutations could lead to the development of a tumor, which means that these tumors produce different antigens and an individual approach is needed for their treatment. Antigens are specific not only for individual types of tumors, but also for a specific tumor in a particular patient.
Based on this, scientists are developing personalized vaccines. Such vaccines are produced individually for each patient. First, immune system cells are extracted from the patient's blood. Then the resulting cells are sent to the laboratory, where they are incubated with an antigen specific to a particular tumor, and special growth factors are added that enhance the immune response. "Advanced" cells that can recognize cancerous cells and destroy them are then injected into the patient.
The first vaccine called Sipuleucel-T based on this principle was approved by the FDA in April 2010 and is used to treat prostate cancer.
In most clinical studies, vaccines are used as an adjunct to traditional therapy. For example, first a tumor is surgically removed, and then a vaccine is used to achieve the complete destruction of all tumor cells. At the same time, it is often possible to increase the effectiveness of treatment, reduce the severity of side effects and improve the quality of life of patients. Some researchers hope that in the future biological therapy will be able to replace traditional methods of treatment. In the meantime, it is only at the very beginning of its development, and time must pass for fundamental discoveries in the field of biology and immunology of tumors to find wide application in clinical medicine.
Portal "Eternal youth" http://vechnayamolodost.ru15.11.2012