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, Joachim L. Schultze

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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.

Original languageEnglish (US)
Pages (from-to)3287-3294
Number of pages8
JournalBlood
Volume102
Issue number9
DOIs
StatePublished - Nov 1 2003

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Maecker, B., Sherr, D. H., Vonderheide, R. H., Von Bergwelt-Baildon, M. S., Hirano, N., Anderson, K. S., Xia, Z., Butler, M. O., Wucherpfennig, K. W., O'Hara, C., Cole, G., Kwak, S. S., Ramstedt, U., Tomlinson, A. J., Chicz, R. M., Nadler, L. M., & Schultze, J. L. (2003). The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells. Blood, 102(9), 3287-3294. https://doi.org/10.1182/blood-2003-05-1374