Tumor necrosis factor (TNF) is a specific protein of the group of cytokines - hormone-like substances produced by the immune system. It causes great interest in medicine due to its properties - the ability to cause cell death (necrosis) of intratumoral tissue. This is a real breakthrough in medicine, allowing the use of drugs with TNF for the treatment of cancer.
Discovery story
By the beginning of the 20th century, a pattern was discovered in medical practice: in some patients, there was a decrease and / or disappearance of tumor formations after undergoing any infection. After that, the American researcher William Coley began to deliberately administer to cancer patients preparations containing an infectious principle (bacteria and their toxins).
The method was not considered effective, as it had a strong toxic effect on the patient’s body. But this was the beginning of a number of studies that led to the discovery of a protein called tumor necrosis factor.
The detected substance caused the rapid death of malignant cells implanted under the skin of experimental mice. A little later pure TNF was isolated, which made it possible to use it for research purposes.
This discovery has contributed to a real breakthrough in cancer therapy. Previously, with the help of protein cytokines, only some oncological formations were successfully treated - skin melanoma, kidney cancer. But a significant advance in this direction was made possible by the study of the properties that the tumor necrosis factor possesses. Drugs based on it are included in the chemotherapy procedure.
Mechanism of action
Tumor necrosis factor acts on a specific target cell. There are several mechanisms of action:
- Through special TNF receptors, a multistage mechanism is launched - programmed cell death (apoptosis). This action is called cytotoxic. In this case, either a complete disappearance of the neoplasm, or a decrease in its size, is observed.
- Through violation or complete cessation of the cell cycle. The cancer cell becomes incapable of division and the growth of the tumor stops. This action is called cytostatic. Usually, the tumor either stops growing or decreases in size.
- By blocking the formation of new vessels of the tumor tissue and damage to existing capillaries. A tumor, devoid of nutrition, necrotizes, decreases and disappears.
There are situations when cancer cells may be insensitive to the drugs administered due to mutations. Then the above mechanisms do not arise.
Use in medicine
Tumor necrosis factor is used in the so-called cytokine therapy - treatment with specific proteins produced by blood cells responsible for immunity. The procedure is possible at any stage of the tumor process and is not contraindicated for people with concomitant pathologies - cardiovascular, renal, and liver. To reduce toxicity, a tumor necrosis factor that is subject to recombination is used.
Cytokine treatment is a new and progressively developing area in oncology. Moreover, the use of TNF is considered the most effective. Since this substance is highly toxic, it is used by the so-called regional perfusion. The method consists in isolating an organ or part of the body infected with a tumor using special equipment from the general bloodstream. Then, blood circulation with TNF administered is artificially started.
Dangerous effects
In medical practice, the tumor necrosis factor is used with caution. A number of studies prove that TNF is a key component in the development of sepsis, toxic shock. The presence of this protein increased the pathogenicity of bacterial and viral infections, which is especially dangerous in the presence of HIV in the patient. It has been proven that TNF is involved in the occurrence of autoimmune diseases (for example, rheumatoid arthritis) in which the immune system mistakenly takes the tissues and cells of your body for foreign bodies and damages them.
To minimize the high toxic effects, the following measures should be observed:
- use only locally at the site of tumor formation;
- combined with other drugs;
- work with mutant less toxic TNF proteins;
- neutralizing antibodies are administered.
These circumstances force the limited use of tumor necrosis factor. Treatment should be properly organized.
Diagnostic indicator
A blood test does not record TNF in a healthy body. But its level increases sharply with infectious diseases, when the toxins of the pathogen enter the bloodstream. Then it can be contained in urine. Tumor necrosis factor in the joint fluid indicates rheumatoid arthritis.
Also, an increase in this indicator indicates allergic reactions, oncological diseases and is a sign of rejection of transplanted donor organs. There is evidence that an increase in this indicator may indicate noncommunicable diseases, for example, heart failure, bronchial asthma.
With various immunodeficiencies (including AIDS) and severe viral diseases, as well as injuries and burns, conditions are created that reduce the tumor necrosis factor. A drug with an immunosuppressive effect will give a similar effect.
Preparations
TNF-based drugs are called targeted drugs - they can act on a specific cancer cell molecule, causing the death of the latter. At the same time, the effect on other organs remains minimal, which reduces the toxicity of the tumor necrosis factor. TNF-based drugs are used both independently (monotherapy), and in combination with other agents.
Today, there are several funds based on TNF, namely:
- NGR-TNF is a foreign drug whose active substance is a derivative of TNF. It can damage the vessels of the tumor, depriving it of nutrition.
- Alnorin is a Russian development. Highly effective in combination with interferons.
"Refnot" - a new Russian drug, contains tumor necrosis factor and thymosin-alpha 1. Its toxicity is extremely low, but its effectiveness is equal to natural TNF and even exceeds it due to the immunostimulating effect. The drug was created in 1990. It successfully passed all the necessary clinical trials and only in 2009 was registered, which gave official permission for the treatment of malignant neoplasms.
Self-administration of any drugs based on the tumor necrosis factor is strictly prohibited. The treatment of cancer is a complex process that takes place exclusively under the supervision of a specialist.