Abstract
BackgroundHuman cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. Despite the fact that the melanoma cell preparations used in a recent vaccine trial (Mel37) were gamma-irradiated (200 Gy), approximately 25% of the preparations failed quality control release criteria which required that the irradiated cells incorporate 3H-thymidine at no more than 5% the level seen in the non-irradiated cells. We have, therefore, investigated ultraviolet (UV)-irradiation as a possible adjunct to, or replacement for gamma-irradiation.MethodsMelanoma 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.ResultsUV-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.ConclusionThese 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.
Highlights
Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated
Proliferation of gamma-irradiated melanoma cells prepared for autologous vaccination Mel37 was an autologous melanoma vaccine trial conducted at the University of Virginia (UVA)
As part of the lot vaccine release criteria, the 3Hthymidine incorporation of the irradiated cells had to be less than 5% of the 3H-thymidine incorporation of the corresponding non-irradiated cells
Summary
Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. 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. Peptide, protein, or DNA-based vaccines currently being tested can potentially stimulate immune responses for which there is no target in a particular patient. Such vaccines designed for use in a general population do not contain unique antigens arising from mutated gene products as these antigens would only be useful in the patient whose tumor expresses them [12,13,14]. Targeting unique antigens might prove advantageous, as many of the altered proteins may play a role in the malignant phenotype of the cell [13,14]
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