TY - JOUR
T1 - The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells
AU - Maecker, Britta
AU - Sherr, David H.
AU - Vonderheide, Robert H.
AU - Von Bergwelt-Baildon, Michael S.
AU - Hirano, Naoto
AU - Anderson, Karen S.
AU - Xia, Zhinan
AU - Butler, Marcus O.
AU - Wucherpfennig, Kai W.
AU - O'Hara, Carl
AU - Cole, Geoffrey
AU - Kwak, Silvia S.
AU - Ramstedt, Urban
AU - Tomlinson, Andy J.
AU - Chicz, Roman M.
AU - Nadler, Lee M.
AU - Schultze, Joachim L.
PY - 2003/11/1
Y1 - 2003/11/1
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2003-05-1374
DO - 10.1182/blood-2003-05-1374
M3 - Article
C2 - 12869499
AN - SCOPUS:0142152431
SN - 0006-4971
VL - 102
SP - 3287
EP - 3294
JO - Blood
JF - Blood
IS - 9
ER -