Upregulation of MHC Class II
Due to the extremely polymorphic nature of MHC class II molecules, simple transfection of these proteins does not provide a practical method for use as a cancer vaccine. (Chamuleau et al., 2006) Alternately, two other methods have been examined to upregulate the expression of these proteins on MHC class II- cells. The first is treatment with IFNγ, which can lead to increased MHC class II expression. (Trincheiri and Perussia, 1985, Fransen L, 1986) A second, more effective approach involves targeting the genes responsible for the synthesis of these proteins, the CIITA or class II transcription activator. Selective gene targeting of CIITA has been used ex vivo to allow MHC class II- cells to become MHC class II+. (Xu, et al. 2000) upregulation of CIITA also causes an increased expression of Ii, and as such, must be used in conjuncture with the antisense techniques referred to earlier. (Qui, 1999) In some forms of cancer, such as acute myeloid leukemia (AML) the cells may already be MHC class II+, but because of mutation, express low, levels on their surface. It is believed that low levels are seen as a direct result of methylation of the CIITA promoter genes (Morimoto et al., 2004, Chamuleau et al., 2006) and that demethylation of these promoters may restore MHC class II expression. (Chamuleau et al., 2006)
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