Autoimmunity and the immunotherapy of cancer: targeting the "self" to destroy the "other".
It is increasingly clear that immunity to "self"-antigens may result in tumor destruction in mouse and man. But which antigens should be targeted with therapeutic cancer vaccines? In the case of melanoma, recognition of melanocyte differentiation antigens (MDA) can be associated with autoimmune depigmentation (vitiligo). We propose that intersection of protein transport to melanosomes and endosomes allows for the loading of MDA-derived peptides on MHC class II molecules, resulting in the activation of MDA-specific CD4+ "helper" T cells that aid the induction of melanoma-specific CD8+ T cells. Thus, the immunogenicity of MDA may be a consequence of their unique cell biology. Studies of MDA-based vaccines can provide new insight into the development of more effective cancer vaccines.
Overwijk
W W
WW
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA.
Restifo
N P
NP
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000276:immunology*; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000627:therapeutic use*; D051379:Mice; D009363:Neoplasm Proteins / Q000627:therapeutic use*; D014820:Vitiligo / Q000276:immunology; D058951:gp100 Melanoma Antigen
D019496:Cancer Vaccines; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; C548642:Pmel protein, mouse; D058951:gp100 Melanoma Antigen