The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells.
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.
Maecker
Britta
B
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
Sherr
David H
DH
Vonderheide
Robert H
RH
von Bergwelt-Baildon
Michael S
MS
Hirano
Naoto
N
Anderson
Karen S
KS
Xia
Zhinan
Z
Butler
Marcus O
MO
Wucherpfennig
Kai W
KW
O'Hara
Carl
C
Cole
Geoffrey
G
Kwak
Silvia S
SS
Ramstedt
Urban
U
Tomlinson
Andy J
AJ
Chicz
Roman M
RM
Nadler
Lee M
LM
Schultze
Joachim L
JL
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*
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