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 tu mor destruction in mouse and man. But which antigens should be targeted wit h therapeutic cancer vaccines? In the case of melanoma, recognition of mela nocyte differentiation antigens (MDA) can be associated with autoimmune dep igmentation (vitiligo). We propose that intersection of protein transport t o 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 ce lls. Thus, the immunogenicity of MDA may be a consequence of their unique c ell biology. Studies of MDA-based vaccines can provide new insight into the development of more effective cancer vaccines.