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Characterization of a single peptide derived from cytochrome P4501B1 that elicits spontaneous human leukocyte antigen (HLA)-A1 as well as HLA-B35 restricted CD8 T-cell responses in cancer patients

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Cytochrome P450 1B1 (CYP1B1) is widely expressed in human malignancies, but silent in most normal tissues. Importantly, the protein is believed to play an important role in the survival and growth of cancer cells in a stressed environment, e.g., as a result of hypoxia or chemotherapy. Thus, targeting of CYP1B1 represents a potentially successful strategy in the treatment of metastatic cancer, e.g., by therapeutic vaccination. Herein, we describe the characterization of a novel peptide from the CYP1B1 protein (CYP240), which is spontaneously recognized by CD8 T cells in cancer patients. Interestingly, the peptide binds to both human Leukocyte antigen (HLA)-A1 and HLA-B35. Hence, peripheral blood lymphocytes from a total of 49 cancer patients (25 melanoma, 13 RCC, and 11 breast cancer; 41 HLA-A1 positive, 8 HLA-B35 positive) were analyzed for reactivity taking advantage of the EliSpot assay. Rare but strong responses were detected in HLA-A1-positive patients, and more frequent responses were detected in HLA-B35-positive patients. No reactivity against the peptide could be detected in healthy donors. Furthermore, we demonstrated that peptide-specific T cells were able to lyze target cells presenting the peptide on the surface. The characterized CYP240 peptide presented herein opens the avenue for more broader recruitment of patients in vaccination trials targeting CYB1B1. (C) 2008 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved
Udgivelsesdato: 2008/4
OriginalsprogEngelsk
TidsskriftHuman Immunology
Vol/bind69
Udgave nummer4-5
Sider (fra-til)266-272
Antal sider6
ISSN0198-8859
StatusUdgivet - 2008

Bibliografisk note

Times Cited: 1ArticleEnglishStraten, P. THerlev Univ Hosp, Dept Hematol, Ctr Canc Immune Therapy, Herlev Ringvej 75, Herlev, DenmarkCited References Count: 28309MSELSEVIER SCIENCE INC360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USANEW YORK

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