Immunotherapy Of Malignant Tumors

There are various passive and active immunological therapies directed against tumor cells. Passive cellular immunotherapy In passive cellular immunotherapy can be directly infused specific effector cells and does not induce or increased in the patient himself. Lymphokine-activated killer cells (LAK cells) are prepared from the patient’s own T-cells, by means of extracting and propagated in a cell culture system under the influence of IL-2. The proliferated LAK cells are the patient then returned through an intravenous transfusion. Animal experiments have shown that LAK cells are more effective against tumor cells than the original endogenous T cells, possibly because of the larger number. Clinical trials with LAK cells are performed in humans. Tumor infiltrating lymphocytes (TIL) have greater tumoricidal activity than LAK cells might. These cells are grown in culture in the same way as LAK cells. However, in this case the precursor cells of T cells obtained from resected tumor tissue exist. This path leads theoretically to a T-cell population, the greater tumor specificity than those obtained from the blood. Recent clinical studies have shown promising results. Genetically modified T cells can express recognize T-cell receptors (TCR), the tumor-associated antigens (TAAs) with a high specificity for tumor cells. This approach is currently being investigated and may provide significant clinical benefit. The results of the first trials are encouraging. Chimeric antigen receptors (CAR) that recognize specific proteins on the surface of tumor cells. This approach has provided in preliminary clinical trials in patients with B-cell leukemia great potential to the test. Unlike TCR T cells that recognize CAR-T cells recognize only relatively large proteins on the surface of tumor cells. Therefore CAR T cells and TCR T cells may represent complementary approaches to cancer therapy. The simultaneous use of interferon enhances expression of (MHC) antigens on tumor cells and thereby enhances the destruction of tumor cells by the effector cells infused. Passive immunotherapy humoral The passive humoral immunotherapy is characterized by the administration of exogenous antibodies. Antilymphocyte serum was used for the treatment of chronic lymphocytic leukemia and T- and B-cell lymphomas and has led to a temporary decrease in lymphocyte counts or lymph node size. Monoclonal anti-tumor antibody can be conjugated, which are transported specifically to the tumor cells in addition to toxins (eg. As ricin, diphtheria toxin) or radioisotopes. Another technique uses antibodies or bispecific antibody linked to one another using an antibody to the tumor cell reacts and a second with a cytotoxic effector cell. This method brings the effector cell close to the tumor cell and thus leads to an increase in activity against the tumor cells. Both techniques are still at an early stage of the trial, so that the potential clinical benefit is uncertain. Active specific immunotherapy To cellular immunity (with the participation of cytotoxic T-cells) in a host, which has formed spontaneously no effective response against a tumor, cause, methods are required which cause an increase in the presentation of tumor antigens to Wirtseffektorzellen. Cellular immunity can be induced against specific, well-defined antigens. There are several ways to stimulate a response of the host, including the gift of peptides, DNA or tumor cells (the host or a different patient). Peptides and DNA are often added together with antigen presenting cells (dendritic cells). These dendritic cells can also be genetically modified to form additional immunostimulants (z. B. granulocyte-macrophage colony-stimulating factor [GM-CSF]). Peptide-based vaccines using peptides from defined tumor-associated antigens. An increasing number of tumor-associated antigens have been identified as targets of T cells in cancer patients that are now being tested in clinical trials. Studies carried out recently have shown that can achieve the strongest responses when tumor-associated antigens are administered using dendritic cells. These cells are taken from the patient, contacted with the desired tumor associated antigen and then intracutaneously returned to elicit an endogenous T-cell response against the tumor-associated antigen. Peptides can also be administered by simultaneous administration of immunogenic adjuvants. DNA vaccines using recombinant DNA encoding the antigenic a specific (defined) protein. The DNA is introduced into viruses injected either directly to the patient or – are introduced into dendritic cells of the patient, which are then returned to the patient – frequently. The DNA expressing the target antigen and induces or enhances the immune response of the patient. Autochthonous tumor cells (cells that have been removed from the patient), after ex vivo treatment (eg. B., radiation treatment with neuraminidase, Haptenkonjugation, hybridization with other cell lines) is returned to the patient. Through this ex vivo treatment, the malignant potential is reduced and increased the antigenic activity. Occasionally, a genetic modulation of tumor cells is performed to produce immunostimulatory molecules (e.g., cytokines such as GM-CSF or IL-2), co-stimulatory molecules such as B7-1 and allogeneic MHC class I molecules. These changes are the attraction of effector molecules and amplify the systemic tumor response. Clinical trials of GM-CSF-modified tumor cells have shown encouraging preliminary results. Allogeneic tumor cells (cells that other patients were removed) were used in patients with acute lymphocytic leukemia or acute myelogenous leukemia. Here, a remission is induced by intensive chemotherapy and radiotherapy. The irradiated allogeneic tumor cells are then injected to a genetic or chemical modification (to increase the immunogenic potential) to the patient. Occasionally patients (BCG) or other adjuvants also Calmette-Guerin bacillus vaccines (immunotherapy of malignant tumors: Non-specific immunotherapy) administered to enhance an immune response against the tumor. In some studies, but not in the majority, prolonged remission periods and improved Reinduktionsraten were reported. A new approach to cancer treatment is the combination of immunotherapy and conventional chemotherapy, the initial success showed (against historical controls) in randomized Phase I and Phase II trials with various cancers, vaccines and chemotherapies. Immunotherapy and target inhibitors of immune responses immune checkpoint blockers are antibodies that target the molecules that are involved in the natural inhibition of the immune response. Several of these antibodies, the cytotoxic T-lymphocyte-associated protein 4 (CTLA4), programmed cell death protein 1 (PD1) and programmed cell death ligand-1 (PD-L1) molecules are aimed have benefit in patients with melanoma and shown non-small cell lung cancer and clinical trials for the treatment of other cancers are studied in phase III. New therapeutic strategies have been developed to achieve immunosuppressive regulatory T-cells, myeloid-derived suppressor cells and indoleamine 2,3-dioxygenase, peroxynitrite and other molecules in the negative regulation (inhibition) the immune response in cancer play a role. Many of these new therapies are currently in Phase I / II clinical trials. Non-specific immunotherapy interferons (IFN-alpha, -beta, -gamma) are glycoproteins having antitumoral and antiviral activity. Depending on the dose interferons can either enhance cellular and humoral immune response or damp. Interferons also inhibit the division and various synthesis processes in a variety of cells. Clinical studies have shown that interferons have anti-tumor activity in various tumors such. Example, in the hairy cell leukemia, chronic myeloid leukemia, in AIDS-associated Kaposi’s sarcoma, non-Hodgkin’s lymphomas, multiple myeloma and ovarian cancer. However, interferons have significant side effects to such. As fever, malaise, leukopenia, alopecia, and myalgia. Certain bacterial adjuvants (BCG and related substances, suspensions of-killed Corynebacterium parvum) have tumoricidal properties. They have been used with or without additional tumor antigens to, usually to treat various types of tumors in parallel with intensive chemotherapy or radiation. For example, direct injection of BCG resulted in tumor tissue to a regression of melanoma and a prolongation of disease-free intervals in superficial bladder cancer. Also the duration of chemotherapy-induced remission in acute myeloid leukemia, ovarian cancer and non-Hodgkin’s lymphomas could be prolonged.

Health Life Media Team

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