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Home > Non-traditional mesothelioma treatment > Immunotherapy

Immunotherapy

One of the most important mesothelioma treatment is immunotherapy.

Immunotherapy is a new type of experimental cancer treatment that is viewed by many to have possible applications in the treatment of mesothelioma, a rare asbestos cancer that has thus far proven to be incurable.

Immunotherapy is treatment with natural substances that the body uses to fight infection and disease. Immunotherapy works by encouraging the body's natural defence system - the immune system - to attack cancer cells. Immunotherapy is really a type of biological therapy. These are a group of treatments that use natural body substances (or drugs that block them) to treat cancer.

Interferon and interleukin 2

Two types of immunotherapy in trials for mesothelioma are interferon and interleukin-2 (also called IL-2 or aldesleukin). Interferon has been used in trials both on its own and in combination with various chemotherapy drugs. The results of the combination treatment haven't been any better than the chemotherapy drugs on their own. More trials have to be done before we know how useful interferon will be in treating mesothelioma.

IL-2 is made naturally as part of the body's immune response. But now it can be made in the laboratory and used in much larger quantities as cancer treatment. IL-2 can be injected directly into the pleural cavity (intrapleurally) or into the bloodstream. Clinical trials using both these methods have shown some success in stage 1 and 2 mesothelioma. Unfortunately most mesothelioma patients are diagnosed at a later stage than this, when this treatment is not very effective.

Like many human malignancies, pleural mesothelioma appears to be resistant to mechanisms of immune-mediated destruction. In "immunogenic" tumors such as malignant melanoma, immunotherapy via exogenous cytokines, monoclonal antibody, and tumor vaccines have demonstrated some significant responses.

Immunotherapy has also been applied to mesothelioma, despite the observations that mesothelioma cells induce intratumoral downregulation of cellular, cytokine, and humoral immune responses, which might significantly inhibit any approaches to augment the antitumor immune response. In particular, high levels of transforming growth factor (TGF) elaborated by mesothelioma cells and tumor-infiltrating macrophages cause downregulation of CD3 molecules on the cell membrane of tumor-infiltrating T lymphocytes, leading to a state of "tolerance" toward the tumor.

Mesothelioma cells express abundant class I major histocompatibility complex molecules but only small amounts of class II, and there is no demonstrable expression of the important costimulatory molecule B71. This results in minimal natural killer cell antitumor activity, poor presentation of tumor antigens to CD4 helper T lymphocytes, and inadequate stimulation of CD8 cytotoxic T lymphocytes.

In addition to the tumor's innate mechanisms of immune evasion, it has been demonstrated that patients with mesothelioma have impaired immune systems: abnormal humoral and cell-mediated immunity, abnormal cell-mediated antibody-dependent cellular toxicity, and defective macrophage and natural killer cell function.

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