Cancer immunotherapy

Cancer immunotherapy and its use in combination with radical methods of treating cancer patients helps improve the effectiveness of treatment, prevent relapses and metastases.

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

Cancer immunotherapy activates cellular antitumor immunity. The main role in the body's antitumor defense is played by a certain group of lymphocytes called natural killers.

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Adoptive immunotherapy for cancer

Natural killers, unlike other lymphocytes, are able to effectively lyse (kill) tumor cells. However, their numbers are small - only 10-15% of all blood lymphocytes, which does not allow them to cope with the tumor mass. To increase the number of killer lymphocytes, so-called adoptive (introduced) cancer immunotherapy is used. The essence of these methods is that ordinary lymphocytes are extracted from the patient's blood, then in laboratory conditions they are treated with special biologically active substances - the so-called lymphokines, obtained using 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 of cancer allows obtaining a significant number of so-called lymphokine-activated killers (LAK) from the patient's normal blood lymphocytes. The latter are introduced into the patient's body, where they exert an antitumor effect.

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

Adoptive immunotherapy of cancer using LAK cells is used mainly to treat so-called immunosensitive forms of malignant neoplasms: melanoma and kidney cancer. In recent years, information has appeared on the use of LAK therapy for other tumors (lung cancer, ovarian cancer, stomach cancer, tumor pleurisy and ascites, etc.).

Currently, cancer immunotherapy is practiced in the adjuvant mode, i.e. after radical operations, chemo- and/or radiation therapy, when it is possible to reduce the tumor mass as much as possible. This allows to extend the duration of the relapse-free period and improve the quality of life of patients.

Cancer immunotherapy enhances the functional activity of the body's immune system cells with the help of cytokines. To do this, the patient's blood is taken, from which the main populations of lymphocytes are isolated. When interleukin-2 and other biogenic substances are added to them in a test tube under sterile conditions, the activity of the isolated cells increases compared to the original, sometimes by tens of times. Following this, the activated cells, ready to fight the tumor, are reintroduced into the patient.

The described cancer immunotherapy using cytokines and LAK cells is aimed at stimulating the non-specific link of antitumor immunity, but one cannot ignore the fact that T-killers, which make up a significant part of the lymphoid cell population and are responsible for the implementation of specific immune mechanisms, remain uninvolved in antitumor protection. Therefore, new immunotherapy methods have recently been developed aimed at creating specific antitumor autovaccines.

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Cancer Immunotherapy with Vaccines

Cancer immunotherapy using vaccines has been developing since the 1980s and is now one of the most promising areas of biotherapy. According to N. Restifo and M. Sznol (1997), it is a method based on the use of any antigen or antigen complex to modulate the immune response.

To stimulate an immune response that "hits" a tumor cell, it is necessary to have special molecules on its surface, called tumor-associated antigens. When such an antigen is isolated from a tumor and then introduced into the patient's body, clones of immune cells are produced to this antigen. "Trained" immunocytes recognize the artificially introduced antigen on tumor cells in the patient's body. Finding a tumor by the target antigen, the immune system destroys it. Thus, the main principle of the vaccine is to teach the immune system to recognize a specific tumor antigen.

The most frequently used vaccines in clinical practice today are BCG, rabies, and smallpox. In case of widespread tumors, the effectiveness of vaccine therapy does not exceed 10%, and in a preventive mode it has practically not been studied. Therefore, at present, this cancer immunotherapy cannot be the "therapy of choice" in oncology. In the near future, its place will be determined.

Researchers working on the problem of creating modern antitumor vaccines face a special task - not just to prepare a vaccine, but to create a vaccine that would ensure the development of specific immunity even if no immune response occurs against a given native antigen (vaccine).

Anti-tumor vaccines are being studied in leading oncology clinics in Europe and Russia. In a number of cases, a positive clinical effect has been observed. This is especially encouraging, since the tests are conducted exclusively on patients with a widespread form of the disease after the ineffective use of traditional treatment methods. According to leading specialists in this field, this method of treatment may be much more effective in prolonging the relapse-free period of life of cancer patients after maximum removal of the tumor mass by surgery, chemotherapy or radiation. Experiments have been conducted on mice, showing the effectiveness of this method in preventing relapse of the disease.

Cancer Immunotherapy Using Monoclonal Antibodies

Cancer immunotherapy also uses monoclonal antibodies that interact with specificity of certain molecular targets in the tumor. A special feature of monoclonal antibodies is that, along with direct blocking of specific pathogenetic mechanisms, they are capable of directly or indirectly inducing antitumor defense reactions in the host organism. Hundreds of antibodies and conjugates are at the research stage of development, and dozens are in the phase of successful preclinical study. A small group of drugs based on monoclonal antibodies are undergoing various phases of clinical trials, and only three antibodies have been approved 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.

Tumor development is associated with the growth of blood vessels that deliver nutrients to the tumor. This phenomenon is called neoangiogenesis. A tumor cannot develop without nutrition, so if the vascularization of tumor tissue is prevented, tumor growth will stop. For this purpose, a monoclonal antibody, bevacizumab, or avastin, was created that blocks the vascular growth factor. Bevacizumab is being studied in breast cancer, colon cancer in combination with chemotherapy, and kidney cancer.

Cancer immunotherapy using monoclonal antibodies is used both in monotherapy and in combination therapy with classical antitumor agents, as well as with interferons and interleukins. Unfortunately, the assessment of the antitumor activity of drugs based on individual monoclonal antibodies is ambiguous. A number of studies have revealed their high efficiency, but randomized studies on large clinical material have not shown the advantages of using antibodies compared to chemotherapy. At the same time, the feasibility of combining antibodies with cytostatics, as well as the use of antibody conjugates with radioactive agents, has been demonstrated.

Cancer Immunotherapy Using Plants

Currently, a new direction is being formed based on increasing the body's reserve capabilities with the help of non-toxic natural bioregulators. Natural bioregulators include herbal remedies with different mechanisms of action on the tumor-bearing organism: phytoadaptogens, antioxidant phytocomplexes, herbal immunomodulators, herbal enterosorbents, vitamin-mineral compositions and herbal interferonogens.

A special place among natural bioregulators is occupied by phytoadaptogens - these are herbal preparations that non-specifically increase the body's resistance to various adverse effects, including carcinogenic agents. Such adaptogens as ginseng, senticosus senticosus, safflower leuzea, Chinese magnolia vine, rose rhodiola, Manchurian aralia, Baikal skullcap and others have a wide therapeutic range and are able to increase the body's resistance to the damaging effects of chemical, physical and biological nature. Adaptogens reduce the incidence of tumors and also extend the latent period of their development. Natural adaptogens have proven to be very effective when used in combination with antitumor cytostatic drugs, helping to reduce toxic effects and reduce metastasis.

In experimental conditions, a number of researchers have found that adaptogens such as ginseng and senticosus can prevent metastasis of malignant neoplasms. There is also evidence that Rhodiola rosea, senticosus, and plantain prevent metastasis after surgery.

Many plants contain immunoactive substances, so they can be used as cancer immunotherapy. Such plants include mistletoe, milky white iris, yellow water lily, blue licorice. There are plants that promote the production of interferon and interleukin (plantain, nettle, couch grass, etc.). Some of these plants are used for malignant tumors of various histogenesis to correct immune disorders.