The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines

BMC Cancer. 2008 Dec 4;8:360. doi: 10.1186/1471-2407-8-360.

Abstract

Background: 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. 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis / radiation effects
  • Blotting, Western
  • Cancer Vaccines*
  • Cell Proliferation / radiation effects
  • Cell Survival / radiation effects
  • Dose-Response Relationship, Radiation
  • Gamma Rays*
  • Humans
  • Immunohistochemistry
  • Melanoma / therapy*
  • Tumor Cells, Cultured / radiation effects*
  • Ultraviolet Rays*

Substances

  • Cancer Vaccines