|
From Wikipedia: Cancer Immunotherapy is the use of the immune system to reject cancer. The main premise is stimulating the patient's immune system to attack the malignant tumor cells that are responsible for the disease. This can be either through immunization of the patient, in which case the patient's own immune system is trained to recognize tumor cells as targets to be destroyed, or through the administration of therapeutic antibodies as drugs, in which case the patient's immune system is recruited to destroy tumor cells by the therapeutic antibodies. Since the immune system responds to the environmental factors it encounters on the basis of discrimination between self and non-self, many kinds of tumor cells that arise as a result of the onset of cancer are more or less tolerated by the patient's own immune system since the tumor cells are essentially the patient's own cells that are growing, dividing and spreading without proper regulatory control. In spite of this fact, however, many kinds of tumor cells display unusual antigens that are either innapropriate for the cell type and/or its environment, or are only normally present during the organisms' development (e.g. fetal antigens). Examples of such antigens include the glycosphingolipid GD2, a disialoganglioside that is normally only expressed at a significant level on the outer surface membranes of neuronal cells, where its exposure to the immune system is limited by the blood-brain barrier. GD2 is expressed on the surfaces of a wide range of tumor cells including neuroblastoma, medulloblastomas, astrocytomas, melanomas, small-cell lung cancer, osteosarcomas and other soft tissue sarcomas. GD2 is thus a convenient tumor-specific target for immunotherapies. Other kinds of tumor cells display cell surface receptors that are rare or absent on the surfaces of healthy cells, and which are responsible for activating cellular signaling pathways that cause the unregulated growth and division of the tumor cell. Examples include ErbB2, a constitutively active cell surface receptor that is produced at abnormally high levels on the surface of breast cancer tumor cells. Antibodies are a key component of the adaptive immune response, playing a central role in both in the recognition of foreign antigens and the stimulation of an immune response to them. It is not surprising therefore, that many immunotherapeutic approaches involve the use of antibodies. The advent of monoclonal antibody technology has made it possible to raise antibodies against specific antigens such as the unusual antigens that are presented on the surfaces of tumors. A number of therapeutic monoclonal antibodies have been approved for use in humans.
this therapeutic consists of the antibody conjugated to the cytotoxic compound calicheamicin
this is a radioimmunotherapeutic consisting of the antibody conjugated to yttrium-90 or indium-111
The development and testing of second generation immunotherapies are already under way. While antibodies targeted to disease-causing antigens can be effective under certain circumstances, in many cases, their efficacy may be limited by other factors. In the case of cancer tumors, the microenvironment is immunosuppressive, allowing even those tumors that present unusual antigens to survive and flourish in spite of the immune response generated by the cancer patient, against his or her own tumor tissue. Certain members of a group of molecules known as cytokines, such as Interleukin-2 also play a key role in modulating the immune response, and have been tried in conjunction with antibodies in order to generate an even more devastating immune response against the tumor. While the therapeutic administration of such cytokines may cause systemic inflammation, resulting in serious side effects and toxicity, a new generation of chimeric molecules consisting of an immune-stimulatory cytokine attached to an antibody that targets the cytokine's activity to a specific environment such as a tumor, are able to generate a very effective yet localized immune response against the tumor tissue, destroying the cancer-causing cells without the unwanted side-effects. A different type of chimeric molecule is an artificial T cell receptor. The targeted delivery of cytokines by anti-tumor antibodies is one example of using antibodies to delivery payloads rather than simply relying on the antibody to trigger an immune response against the target cell. Another strategy is to deliver a lethal radioactive dose directly to the target cell, which has been utilized in the case of the Zevalin® therapeutic. A third strategy is to deliver a lethal chemical dose to the target, as used in the Mylotarg® therapeutic. Engineering the antibody-payload pair in such a way that they separate after entry into a cell by endocytosis can potentially increase the efficacy of the payload. One strategy to accomplish this is the use of a disulfide linkage which could be severed by the reducing conditions in the cellular interior. However, recent evidence suggests that the actual intracellular trafficking of the antibody-payload after endocytosis is such to make this strategy not generally applicable. Other potentially useful linkage types include hydrazone and peptide linkages. Dermatologists use new creams and injections in the management of benign and malignant skin tumors. Topical immunotherapy utilizes a immune enhancement cream (imiquimod) which is an interferon producer causing the patient's own killer T cells to destroy warts, actinic keratoses, basal cell cancer, squamous cell cancer, cutaneous lymphoma, and superficial malignant melanoma. Injection immunotherapy uses mumps, candida or trichophytin antigen injections to treat warts (HPV induced tumors).
This website is sponsored by Brad Cooper* of The
Cooper, Hart, Leggiero, & Whitehead, PLLC. Cooper, Hart, Leggiero, & Whitehead is located in The Woodlands, Texas
(Greater Houston Area) and can be reached toll free at 1-800-998-9729
for more information on mesothelioma. Brad Cooper is not a medical
doctor. The information on these pages is for the education of mesothelioma
patients and their families regarding potential medical and legal
options. Patients are advised to consult with a medical doctor.
|
The
use of chemotherapy in patients with advanced malignant pleural mesothelioma:
a clinical practice guideline.
|