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

Pia Kvistborg, Sine Reker Hadrup, Inge Marie Svane, Mads Hald Andersen, Per thor Straten

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.
Original languageEnglish
JournalHuman Immunology
Volume69
Issue number4-5
Pages (from-to)266-272
Number of pages7
ISSN0198-8859
DOIs
Publication statusPublished - 2008
Externally publishedYes

Keywords

  • Immunology
  • Immunology and Allergy
  • Cancer
  • CD8 T cell
  • Cytochrome P450 1B1
  • HLA-A1
  • HLA-B35
  • Tumor associated antigen (TAA)
  • cytochrome P450
  • HLA A1 antigen
  • HLA B35 antigen
  • amino acid sequence
  • article
  • breast cancer
  • cancer patient
  • CD8+ T lymphocyte
  • clinical article
  • controlled study
  • enzyme linked immunospot assay
  • human
  • human cell
  • melanoma
  • peripheral lymphocyte
  • priority journal
  • Amino Acid Sequence
  • Antigens, Neoplasm
  • CD8-Positive T-Lymphocytes
  • Cytochrome P-450 Enzyme System
  • Cytotoxicity Tests, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HLA-A1 Antigen
  • HLA-B35 Antigen
  • Humans
  • Immunity, Cellular
  • Neoplasms
  • Oligopeptides
  • CANCER treatment
  • Aryl Hydrocarbon Hydroxylases
  • 9035-51-2 Cytochrome P-450 Enzyme System
  • EC 1.14.14.1 Aryl Hydrocarbon Hydroxylases
  • EC 1.14.14.1 cytochrome P-450 CYP1B1
  • IMMUNOLOGY
  • ELISPOT ASSAY
  • IDENTIFICATION
  • LYMPHOCYTES
  • IMMUNITY
  • PROTEIN
  • CYP1B1
  • EXPRESSION
  • P450CYP1B1
  • RESISTANCE
  • tumor associated antigen (TAA)
  • cytochrome P4501B1
  • cancer
  • cancer Neoplasms (MeSH) neoplastic disease
  • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common
  • cytochrome P450 1B1 330596-22-0
  • human leukocyte antigen-A1
  • human leukocyte antigen-B35
  • 10060, Biochemistry studies - General
  • 15002, Blood - Blood and lymph studies
  • 15004, Blood - Blood cell studies
  • 24003, Neoplasms - Immunology
  • 24004, Neoplasms - Pathology, clinical aspects and systemic effects
  • 34502, Immunology - General and methods
  • 34508, Immunology - Immunopathology, tissue immunology
  • Human Medicine, Medical Sciences
  • CD8 T-cells immune system, blood and lymphatics
  • Biochemistry and Molecular Biophysics
  • Clinical Immunology
  • Oncology
  • RUMBELOW, Andrew

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