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Immunogenicity of Constitutively Active V599EBRaf

2004; American Association for Cancer Research; Volume: 64; Issue: 15 Linguagem: Inglês

10.1158/0008-5472.can-04-0937

1538-7445

Mads Hald Andersen, Joachim Fensterle, Selma Ugurel, Sine Reker, Roland Houben, Per Guldberg, Thomas G. Berger, Dirk Schadendorf, Uwe Trefzer, Eva‐B. Bröcker, Per thor Straten, Ulf R. Rapp, Jürgen C. Becker,

CAR-T cell therapy research

Abstract Activating BRAF somatic missense mutations within the kinase domain are present in 60–66% of melanomas. The vast majority of these represent a single substitution of glutamate for valine (V599E). Here, we demonstrate spontaneous HLA-B*2705-restricted cytotoxic T-cell responses against an epitope derived from V599EBRaf. These T-cell responses were mutation specific as the corresponding epitope derived from wild-type BRaf was not recognized. The loss of the V599EBRAF genotype during progression from primary to metastatic melanoma in patients with V599EBRaf specific T-cell responses suggests an active immune selection of nonmutated melanoma clones by the tumor-bearing host.