Characterization of a single peptide derived from Cytochrome P450 1B1 that elicits spontaneous HLA-A1 as well as HLA-B35 restricted CD8 T-cell responses in cancer patients
Cytochrome P450 1B1 (CYP1B1) is widely expressed in human malignancies, but silent in most normal other tissues. Importantly, the protein is believed to play an important role for the survival and growth of cancer cells in a stressed environment, e.g., due to hypoxia or chemotherapy. Thus, targeting of CYP1B1 represents a potentially successful strategy in the treatment of metastatic cancer, e.g., by therapeutic vaccination. Herein, we describe the characterization of a novel peptide from the CYP1B1 protein (CYP240), which is spontaneously recognized by CD8 T cells in cancer patients. Interestingly, the peptide binds to both HLA-A1 and HLA-B35. Hence, peripheral blood lymphocytes from a total of 49 cancer patients (25 melanoma, 13 RCC, and 11 breast cancer; 41 being HLA-A1 positive, 8 being HLA-B35 positive,) were analyzed for reactivity taking advantage of the EliSpot assay. Rare but strong responses were detected in HLA-A1 positive patients, and more frequent responses were detected in HLA-B35 positive patients. No reactivity against the peptide could be detected in healthy donors. Furthermore, we showed that peptide specific T cells were able to lyze target cells presenting the peptide on the surface. The characterized CYP240 peptide presented herein, opens the avenue for more a broad recruitment of patients in vaccination trials targeting CYB1B1.
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