title: The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells.
abstract: Cytochrome P450 1B1 (CYP1B1), a drug-metabolizing extrahepatic enzyme, was recently shown to be overexpressed in multiple types of cancer. Such tumor-associated genes may be useful targets for anticancer therapy, particularly cancer immunotherapeutics. We identified HLA-A*0201-binding peptides and a naturally processed and presented T-cell epitope capable of inducing CYP1B1-specific cytotoxic T lymphocytes (CTLs) in HLA-A2 transgenic mice. Furthermore, the induction of CYP1B1-specific T cells was demonstrated in healthy donors and cancer patients. These T cells efficiently lysed target cells pulsed with the cognate peptide. More important, HLA-A2-matched tumor cell lines and primary malignant cells were also recognized by CYP1B1-specific CTLs. These findings form the basis of a phase 1 clinical trial exploring a DNA-based vector encoding CYP1B1 for widely applicable cancer immunotherapy conducted at the Dana-Farber Cancer Institute.
authors.affiliation: Head, Molecular Tumor Biology and Tumor Immunology University of Cologne, Joseph-Stelzmann Str. 9/Haus 16, 50924 Cologne, Germany. joachim.schultze@medizin.uni-koeln.de
authors.forename: Britta
authors.initials: B
authors.lastname: Maecker
authors.forename: David H
authors.initials: DH
authors.lastname: Sherr
authors.forename: Robert H
authors.initials: RH
authors.lastname: Vonderheide
authors.forename: Michael S
authors.initials: MS
authors.lastname: von Bergwelt-Baildon
authors.forename: Naoto
authors.initials: N
authors.lastname: Hirano
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Xia
authors.forename: Marcus O
authors.initials: MO
authors.lastname: Butler
authors.forename: Kai W
authors.initials: KW
authors.lastname: Wucherpfennig
authors.forename: Carl
authors.initials: C
authors.lastname: O'Hara
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Cole
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Kwak
authors.forename: Urban
authors.initials: U
authors.lastname: Ramstedt
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Tomlinson
authors.forename: Roman M
authors.initials: RM
authors.lastname: Chicz
authors.forename: Lee M
authors.initials: LM
authors.lastname: Nadler
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000276:immunology*; D001773:Blood Cells; D045744:Cell Line, Tumor; D065633:Cytochrome P-450 CYP1B1; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010455:Peptides; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; C585498:Cyp1b1 protein, mouse; D065633:Cytochrome P-450 CYP1B1