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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3287-3294.
Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2003-05-1374.
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IMMUNOBIOLOGY
The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells
Britta Maecker,
David H. Sherr,
Robert H. Vonderheide,
Michael S. von Bergwelt-Baildon,
Naoto Hirano,
Karen S. Anderson,
Zhinan Xia,
Marcus O. Butler,
Kai W. Wucherpfennig,
Carl O'Hara,
Geoffrey Cole,
Silvia S. Kwak,
Urban Ramstedt,
Andy J. Tomlinson,
Roman M. Chicz,
Lee M. Nadler, and
Joachim L. Schultze
From the Department of Adult Oncology and the Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston; Department of Medicine, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston; Department of Environmental Health and Department of Pathology and Laboratory Medicine, Boston University School of Public Health; Zycos Inc, Lexington, MA; and the Department for Hematology and Oncology, University of Cologne, Germany.
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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