Idh1 mutations as a immunotherapeutic target for brain tumors.
Immunotherapy promises an exquisitely precise therapeutic approach, and substantial evidence suggests that activated T cells can eradicate large tumors, even within the "immunologically privileged" brain. EGFRvIII and isocitrate dehydrogenase 1 (IDH1) mutations are two of the only consistent tumor-specific mutations that have been described. IDH1 is an evolutionarily-conserved enzyme essential to cell function. Greater than 90% of all IDH1 mutations occur from a substitution of histidine for arginine at codon 132, resulting in the highly conserved and tumor-specific mutation, IDH1R132H. IDH1R132H is homogeneously expressed in all tumor cells in tumors that express this mutation, including single infiltrating tumor cells but is absent in normal cells. The high frequency, specificity, and homogeneous expression of the IDH1 mutation make it an ideal target for therapeutic intervention.
Archer, GE; Reap, E; Norberg, P; Cui, X; Schmittling, R; Herndon, J; Chandramohan, V; Riccione, K; Kuan, CT; Yan, H; Bigner, DD; Sampson, JH
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