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BMC Cancer 2008
The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccinesAbstract: Melanoma cells were gamma- and/or UV-irradiated. 3H-thymidine uptake was used to assess proliferation of the treated and untreated cells. Caspase-3 activity and DNA fragmentation were measured as indicators of apoptosis. Immunohistochemistry and Western blot analysis was used to assess antigen expression.UV-irradiation, either alone or in combination with gamma-irradiation, proved to be extremely effective in controlling the proliferation of melanoma cells. In contrast to gamma-irradiation, UV-irradiation was also capable of inducing significant levels of apoptosis. UV-irradiation, but not gamma-irradiation, was associated with the loss of tyrosinase expression. Neither form of radiation affected the expression of gp100, MART-1/MelanA, or S100.These results indicate that UV-irradiation may increase the safety of autologous melanoma vaccines, although it may do so at the expense of altering the antigenic profile of the irradiated tumor cells.Cellular immune responses to autologous tumor cells have been documented in cancer patients including those with melanoma. Antigens recognized by tumor-specific T cells have been categorized as cancer-testis antigens, differentiation proteins, mutated gene products, widely expressed proteins, and viral proteins [1-3]. Vaccines incorporating synthetic forms of these antigens may be immunogenic, but the ensuing immune response can only be effective if the tumor in the vaccine recipient expresses one or more of the antigens present in the vaccine. This can be problematic because cancer-testis antigens are expressed only in a subset of tumors [4,5]. and differentiation antigens are often down-regulated in metastases [6-11]. Thus, peptide, protein, or DNA-based vaccines currently being tested can potentially stimulate immune responses for which there is no target in a particular patient. Further, such vaccines designed for use in a general population do not contain unique antigens arising from mutated gene products as these antigens w
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