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The Aryl Hydrocarbon (Dioxin) Receptor/Transcription Factor and Cytochrome P450 1B1 as Targets for Breast Cancer Immunotherapy

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Final rept. 1 Sep 2001-31 Aug 2002

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Recent clinical successes have fostered renewed optimism among tumor immunologists. We exploited recent advances to identify immunogenic peptides from self proteins and to present those peptides to generate breast tumor-specific CD8 killer T cell CTL in vitro. Two target proteins, the aryl hydrocarbon receptortranscription factor AhR and the AhR-regulated cytochrome P45O CYPlBl enzyme, were selected for these studies because of their high level expression in breast tumors and their role in environmental chemical carcinogenesis. Three computer-based algorithms identified AhR- and CYPlBl peptides predicted to bind a common human HLA class 1 allele, HLA-A020l. HLA stabilization experiments confirmed high affinity binding of several AhR and CYPlBl peptides to HLA-AO2Ol. Presentation of these peptides on activated B cells to autologous human CD8 T cells in vitro induced CTL which lysed tumors expressing AhR or CYPlBl in an antigen- and HLA-class 1-specific manner CTL frequency analysis with fluorescent peptideHLAAO2Ol tetramers indicated that l-4 of the CD8 T cell population generated in vitro was responsible for the killing activity Enrichment of the peptideHLA-AO2Ol-specific T cells significantly enriched the killing activity The data demonstrate the feasibility of developing breast cancer vaccines with a platform that combines bioinformatics and advanced strategies for tumor antigen presentation.

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  • Biochemistry
  • Medicine and Medical Research

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