title: Cancer stem cell antigen-based vaccines: the preferred strategy for active specific immunotherapy of metastatic melanoma?
abstract: BACKGROUND
  There are now two chemotherapy agents, one tyrosine kinase inhibitor and three immunotherapy products approved for the treatment of metastatic melanoma, but an unmet need persists because these options are toxic and of limited therapeutic benefit. Active specific immunotherapy with therapeutic vaccines could be a useful addition to the therapeutic armamentarium, especially in patients whose tumor burden has been reduced by other treatment modalities.
  
  
  METHODS
  This article reviews various sources of melanoma antigens, such as peptides, gangliosides, autologous tumor and cancer stem cells including allogeneic and autologous cell lines. The advantages and disadvantages of various antigen sources and allogeneic and autologous approaches are discussed with an emphasis on the theoretical benefits of immunizing against cancer stem cells. The results from published randomized trials testing the benefit of various vaccine approaches are summarized, as well as promising results from three Phase II trials (one randomized) of patient-specific stem cell antigen-based products.
  
  
  CONCLUSIONS
  Immune responses directed toward the unique neoantigens and stem cell antigens expressed on continuously proliferating, self-renewing, autologous tumor cells could potentially overcome the limitations inherent in these other antigen-based approaches, that to date, have yielded disappointing results in randomized trials.
authors: Hoag Institute for Research and Education, Hoag Hospital, One Hoag Dr, Bldg 44 Suite 210, Newport Beach, California 92663, USA. robert.dillman@hoag.org
authors: Robert O
authors: RO
authors: Dillman
authors: Andrew N
authors: AN
authors: Cornforth
authors: Gabriel
authors: G
authors: Nistor
mesh_terms: D000276:Adjuvants, Immunologic; D000938:Antigen-Presenting Cells / Q000187:drug effects; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D049109:Cell Proliferation; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008545:Melanoma / Q000628:therapy*; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines