In this paper we describe the key molecular mechanisms and agents targeting them. Melanoma, immune system and free targeting monoclonal rpern Mainly there Ltigende evidence that melanoma is a cancer of the immune system is sensitive. Spontaneous regression of melanoma observed and is likely to the immune system processes. The identification of tumor-infiltrating lymphocytes and melanoma cells in antigen-specific T peripheral blood of cancer patients are evidence that melanoma-specific immune recognition and INO-1001 activation occur.6 8 Au Addition melanoma cell having properties, by the immune system selection, as the down-regulation of Haupthistokompatibilit tskomplex class I expression and the release of cytokines such as transforming growth factor beta.
9, 10 After all, explained AZD6244 dramatic clinical responses have been explained in more detail with hlten immunemodulatory proven treatments, such as IL-2 and adoptive transfer of T cells Selected metastatic melanoma patients, although none of these treatments provide the superiority of the standard of care in randomized clinical trials.4, 11 have shown, however, ipilimumab, a novel monoclonal antique body modulate the immune system the first evidence that a strategy of immunotherapy may be the clinical outcome in metastatic melanoma change and improve patient care survival.12, 13 ipilimumab a modulator of immune activation. The T-cell activation occurs when a stimulatory antigen Haupthistokompatibilit Tskomplex molecule and a molecular co pr Is presents, B7.1 or B7.2 binds CD28.14 Simultaneously, the negative regulation of this process is B7 by cytotoxic T-lymphocytes initiated-associated antigen 4-binding.
Inhibitory receptors and canals schr le co Nken the functions of T lymphocytes for Autoimmunit Prevent t. In cancer patients, prevents Restrict t Restriction antitumor immunity. Monoclonal rpern Which bind to CTLA 4 and blocking the interaction between B7 and CTLA 4 inhibit this negative signal, and can be peripheral tolerance to break tissue and induce antitumor autoimmune response. Ipilimumab is a human good, IgG1 monoclonal antique Body, CTLA fourth By inhibiting CTLA 4 potentiates ipilimumab T cell activation and proliferation, the F Promotion Tumorimmunit t. Proof of benefit of the approach lies in two recent embroidered Les randomized phase III better survival rate in patients with metastatic melanoma treated with ipilimumab.
12, 13, however, showed the drug tumor specific, the effect of s on immune response not: ipilimumab treatment with serious and potentially t dlichen immunological side effects brought by T-cell activation and proliferation. Risk assessment and mitigation strategies have been introduced to the prescribing physicians The m Informing adjusted risks. Phase III randomized study of ipilimumab in patients with advanced melanoma who progressed on standard therapy, zus Addition on receiving ipilimumab gp100, ipilimumab alone or gp100 alone.12 The median overall survival was statistically significant h Forth in patients randomized to with one arm with ipilimumab, compared with patients who gp100 alone. No difference in OS was observed between the ipilimumab groups. This is the first study to demonstrate a survival advantage in advanced melanoma in more than three decades, but the enthusiasm was tempered by the lack of a standard treatment arm stitched on.