Characterization of a single peptide derived from cytochrome P450 1B1 that elicits spontaneous human leukocyte antigen (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 tissues. Importantly, the protein is believed to play an important role in the survival and growth of cancer cells in a stressed environment, e.g., as a result of 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 human leukocyte antigen (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 HLA-A1 positive, 8 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 demonstrated 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 broader recruitment of patients in vaccination trials targeting CYB1B1.
Kvistborg
Pia
P
Dandritt Biotech, Symbion Science Park, Fruebjergvej 3, 2100 Copenhagen, Denmark.
Hadrup
Sine Reker
SR
Svane
Inge Marie
IM
Andersen
Mads Hald
MH
Straten
Per Thor
PT
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology*; D001189:Aryl Hydrocarbon Hydroxylases; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015788:HLA-A1 Antigen / Q000276:immunology*; D015797:HLA-B35 Antigen / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D009369:Neoplasms / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology
D000951:Antigens, Neoplasm; D015788:HLA-A1 Antigen; D015797:HLA-B35 Antigen; D009842:Oligopeptides; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1