PMID- 18486761
OWN - NLM
STAT- MEDLINE
DCOM- 20080721
LR  - 20141120
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 69
IP  - 4-5
DP  - 2008 Apr-May
TI  - Characterization of a single peptide derived from cytochrome P450 1B1 that 
      elicits spontaneous human leukocyte antigen (HLA)-A1 as well as HLA-B35 
      restricted CD8 T-cell responses in cancer patients.
PG  - 266-72
LID - 10.1016/j.humimm.2008.02.007 [doi]
AB  - 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.
FAU - Kvistborg, Pia
AU  - Kvistborg P
AD  - Dandritt Biotech, Symbion Science Park, Fruebjergvej 3, 2100 Copenhagen, Denmark.
FAU - Hadrup, Sine Reker
AU  - Hadrup SR
FAU - Svane, Inge Marie
AU  - Svane IM
FAU - Andersen, Mads Hald
AU  - Andersen MH
FAU - Straten, Per Thor
AU  - Straten PT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080404
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HLA-A1 Antigen)
RN  - 0 (HLA-B35 Antigen)
RN  - 0 (Oligopeptides)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (CYP1B1 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1B1)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigens, Neoplasm/*immunology
MH  - Aryl Hydrocarbon Hydroxylases
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cytochrome P-450 CYP1B1
MH  - Cytochrome P-450 Enzyme System/*immunology
MH  - Cytotoxicity Tests, Immunologic
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - HLA-A1 Antigen/*immunology
MH  - HLA-B35 Antigen/*immunology
MH  - Humans
MH  - Immunity, Cellular
MH  - Neoplasms/*immunology
MH  - Oligopeptides/immunology
EDAT- 2008/05/20 09:00
MHDA- 2008/07/22 09:00
CRDT- 2008/05/20 09:00
PHST- 2008/01/02 00:00 [received]
PHST- 2008/02/01 00:00 [revised]
PHST- 2008/02/08 00:00 [accepted]
PHST- 2008/05/20 09:00 [pubmed]
PHST- 2008/07/22 09:00 [medline]
PHST- 2008/05/20 09:00 [entrez]
AID - S0198-8859(08)00034-7 [pii]
AID - 10.1016/j.humimm.2008.02.007 [doi]
PST - ppublish
SO  - Hum Immunol. 2008 Apr-May;69(4-5):266-72. doi: 10.1016/j.humimm.2008.02.007. Epub 
      2008 Apr 4.