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Blood. 2003 Nov 1;102(9):3287-94. Epub 2003 Jul 17.

The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells.

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1
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

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.

PMID:
12869499
DOI:
10.1182/blood-2003-05-1374
[Indexed for MEDLINE]
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