Immunotherapy of cancer

Immunotherapy of cancer and its use in combination with radical methods of treatment of cancer patients helps improve the effectiveness of treatment, prevention of relapses and metastases.

In recent years, immunotherapy for cancer has been intensively developing, which is one of the most promising areas in oncology. This - the treatment of tumors with the help of various biologically active substances - includes the use of monoclonal antibodies, antitumor vaccines, cytokines, activated lymphocytes, etc.

Immunotherapy of cancer activates cellular antitumor immunity. The main role in the antitumor protection of the body is played by a certain group of lymphocytes called natural killers (killers).

[1], [2], [3], [4]

Adoptive immunotherapy for cancer

Natural killers, unlike other lymphocytes, are able to effectively lyse (kill) tumor cells. However, their number is small - only 10-15% of all blood lymphocytes, which does not allow them to cope with the tumor mass. To increase the number of lymphocyte killers, the so-called adoptive (immunized) cancer is used. The essence of these methods lies in the fact that ordinary lymphocytes are extracted from the patient's blood, then under laboratory conditions they are treated with special biologically active substances - the so-called lymphokines, obtained with the use of genetic engineering technologies. These artificially obtained substances are synthetic analogues of natural lymphokines synthesized in the body and involved in the processes of regulation and activation of immunity.

Thus, adoptive immunotherapy for cancer allows a patient to get a significant number of so-called lymphokine-activated killers (LAC) from normal blood lymphocytes. The latter are introduced into the patient's body, where they have an antitumor effect.

LAC immunotherapy of cancer expands the range of possibilities of antitumor therapy. In addition, it has several advantages over chemotherapy and radiation: the absence of toxicity and good tolerability, the possibility of using together with traditional methods of treatment, as well as in cases of drug resistance, stimulation of local antitumoral cellular immunity, leading to lysis of the tumor, improvement of quality and duration life of patients.

Adoptive cancer immunotherapy with LAC cells is used mainly to treat the so-called immunosensitive forms of malignant neoplasms: melanoma and kidney cancer. In recent years, there have been reports of the use of LAK-therapy in other tumors (lung cancer, ovaries, stomach, with tumor pleurisy and ascites, etc.).

Currently, cancer immunotherapy is administered in adjuvant mode, i.e. After radical surgery, chemo- and / or radiation treatment, when it is possible to minimize the tumor mass as much as possible. This allows you to extend the duration of the disease-free period, improve the quality of life of patients.

Immunotherapy of cancer enhances the functional activity of the cells of the body's immune system with the help of cytokines. For this, the patient takes blood, from which the main populations of lymphocytes are isolated. When added to test tubes under sterile conditions of interleukin-2 and other nutrients, the activity of isolated cells increases in comparison with the initial one sometimes by a factor of tens. After this, the activated cells, ready to fight the tumor, are again administered to the patient.

The described cancer immunotherapy with the use of cytokines and LAK cells is aimed at stimulating the nonspecific link of antitumor immunity, but one can not ignore the fact that T-killers, which constitute a significant part of the population of lymphoid cells and are responsible for the realization of specific immune mechanisms, are not involved in antitumor protection. Therefore, recently developing new methods of immunotherapy, aimed at creating specific antitumor autovaccines.

[5], [6], [7], [8], [9], [10], [11], [12], [13], [14]

Immunotherapy of cancer with vaccines

Immunotherapy of cancer using vaccines began to develop since the 1980s. And is now one of the most promising areas of biotherapy. According to the definition of N.Restifo and M.Znola (N.Restifo, M.Sznol, 1997), this is a method based on the use of any antigen or antigen complex for modulating the immune response.

To stimulate the immune response that "beats" the tumor cell, it is necessary to have special molecules on its surface, called tumor-associated antigens. With the isolation of such an antigen from the tumor and subsequent introduction into the patient's body, the clones of immune cells are produced to this antigen. The "trained" immunocytes on an artificially implanted antigen recognize it on tumor cells in the patient's body. Finding a tumor on the target antigen, the immunity destroys it. Thus, the main principle of the vaccine is to teach the immune system to recognize a specific tumor antigen.

Most often at present in clinical practice, BCG vaccine, rabies vaccine, anti-acute vaccine are used. With widespread tumors, the effectiveness of vaccine therapy does not exceed 10%, and in the preventive regimen it has not been studied. Therefore, at present, this immunotherapy for cancer can not be a "therapy of choice" in oncology. In the near future its place will be determined.

Before the researchers working on the problem of creating modern anti-cancer vaccines, it is a special task - not just to prepare the vaccine, but to create a vaccine that would ensure the development of specific immunity even if no immune response arises against this native antigen (vaccine).

Antitumor vaccines are being studied in leading oncological clinics in Europe and Russia. In a number of cases, a positive clinical effect was observed. This is especially encouraging, since tests are conducted exclusively on patients with a common form of the disease after inefficient use of traditional methods of treatment. According to the leading specialists of this direction, this method of treatment may be much more effective for prolonging the disease-free period of life of cancer patients after maximal removal of the tumor mass by surgical means, with the help of chemotherapy or irradiation. Experiments were conducted in mice that showed the effectiveness of this method for preventing recurrence of the disease.

Immunotherapy of cancer using monoclonal antibodies

Immunotherapy of cancer also uses monoclonal antibodies that interact with specific molecular targets in the tumor with high specificity. A feature of monoclonal antibodies is that, together with direct blocking of specific pathogenetic mechanisms, they are capable of directly or indirectly inducing antitumor protection reactions of the host organism. Hundreds of antibodies and conjugates are at the research stage of development, dozens - at the phase of successful preclinical study. A small group of drugs based on monoclonal antibodies undergoes various phases of clinical trials and only three antibodies are allowed for clinical use in the treatment of lymphomas (rituximab, MabThera), gastrointestinal tumors (endrecolomab, panorex) and breast cancer (trastuzumab, herceptin). Herceptin has revolutionized the treatment of hormone-resistant forms of breast cancer, increasing the effectiveness of chemotherapy.

The development of the tumor is associated with the growth of blood vessels, through which nutrients are delivered to the tumor. This phenomenon is called neoangiogenesis. The tumor can not develop without receiving nutrition, therefore, if vascularization of the tumor tissue is prevented, tumor growth will cease. For this, a monoclonal antibody, bevacizumab, or avastin, a blocking vascular growth factor, has been created. Bevacizumab is being studied in breast cancer, colon cancer in combination with chemotherapy, kidney cancer.

Immunotherapy of cancer using monoclonal antibodies is used both in mono-mode and in combined treatment with classical antitumor agents, as well as with interferons and interleukins. Unfortunately, the evaluation of the antitumor activity of drugs based on individual monoclonal antibodies is ambiguous. A number of studies have shown their high efficacy, but randomized studies on large clinical material did not show the benefits of using antibodies compared to chemotherapy. At the same time, the expediency of combining antibodies with cyto-statics, as well as the use of conjugates of antibodies with radioactive agents, was demonstrated.

Immunotherapy of cancer using plants

At present, a new direction is being formed, based on increasing the reserve capacity of the body with the help of non-toxic natural bioregulators. Natural herbal remedies include herbal remedies with a different mechanism of action on the tumor-forming organism: phytoadaptogens, antioxidant phytocomplexes, plant immunomodulators, plant enterosorbents, vitamin-mineral compositions and plant interferonogens.

A special place among natural bioregulators is occupied by phytoadaptogens - these are herbal preparations that nonspecifically increase the resistance of the organism to various adverse effects, including carcinogenic agents. Such adaptogens as ginseng, eleutherococcus spiny, levsea safflower, magnolia vine, rhodiola rosea, aralia manchurian, skullcap Baikal and others have a great therapeutic breadth and are able to increase the resistance of the organism to the damaging effect of chemical, physical and biological nature. Adaptogens reduce the frequency of development of tumors, and also lengthen the latent period of their development. Natural adaptogenes proved to be very effective when combined with their application with antitumor cytostatic drugs, contributing to the reduction of toxic effects and reducing metastasis.

Under the experimental conditions, a number of researchers have found that adaptogens such as ginseng, eleutherococcus spiny can prevent metastasis of malignant tumors. There are also reports that rhodiola rosea, Eleutherococcus spiny, plantain prevent metastasis after surgery.

Many plants contain immunoactive substances, so they can be used as immunotherapy for cancer. Such plants include the mistletoe white, milk-white millet, yellow egg capsule, licorice blue. There are plants that promote the production of interferon and interleukin (plantain, nettle, wheat grass, etc.). Some of these plants are used in malignant tumors of different histogenesis to correct immune disorders.