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

نویسندگان

  • 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
چکیده

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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عنوان ژورنال:
  • Blood

دوره 102 9  شماره 

صفحات  -

تاریخ انتشار 2003