PMID- 17589290
OWN - NLM
STAT- MEDLINE
DCOM- 20070817
LR  - 20221109
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 30
IP  - 5
DP  - 2007 Jul-Aug
TI  - Cyclin-dependent kinaselike 5 is a novel target of immunotherapy in adult T-cell 
      leukemia.
PG  - 499-505
AB  - In the present study, we attempted a comprehensive analysis of human leukocyte 
      antigen (HLA) class I-bound peptides presented on adult T-cell leukemia (ATL) 
      cells by the latest technology of mass spectrometry combined with reversed phase 
      liquid chromatography (LC/MS) to identify novel tumor-associated antigens. We 
      screened the sequenced peptides for those compatible with the motives of the 
      respective HLA class I alleles. Then, we narrowed down the candidate peptides 
      according to the differential expression of their source proteins between ATL 
      cells and normal CD4 T cells. Among these candidates, we focused on 
      cyclin-dependent kinaselike 5 (CDKL5) because it was highly expressed in several 
      ATL cell lines and some ATL clinical samples but not in normal CD4 T cells. To 
      examine its immunogenicity, we stimulated CD8 T cells from an HLA-B62 healthy 
      donor several times with autologous monocyte-derived dendritic cells loaded with 
      HLA-B*62-restricted CDKL5 peptide1012-1021 QVNQAALLTY that we identified. 
      CDKL5-stimulated bulk CD8 T cells exerted higher cytotoxicity against CDKL5 
      peptide-loaded autologous Epstein Barr virus-transformed B cell line (LCL) than 
      against unloaded LCL. Furthermore these T cells had strong cytotoxic activity 
      against HLA-B*62-positive CDKL5-positive but not HLA-B*62-negative CDKL5-positive 
      ATL cells. These results demonstrate that CDKL5 is a novel tumor (leukemia) 
      antigen in ATL and that the HLA-B*62-restricted CDKL5 peptide can be used for 
      cytotoxic T-lymphocyte-mediated immunotherapy. Identification of tumor-associated 
      antigens by LC/MS is an eligible and efficient method suitable for future 
      taylor-made immunotherapy of hematologic malignancies.
FAU - Kawahara, Masahiro
AU  - Kawahara M
AD  - Department of Hematology and Oncology, Graduate School of Medicine, Kyoto 
      University, 54 Shogoin-Kawaracho, Sakyo, Kyoto 606-8507, Japan.
FAU - Hori, Toshiyuki
AU  - Hori T
FAU - Matsubara, Yasushi
AU  - Matsubara Y
FAU - Okawa, Katsuya
AU  - Okawa K
FAU - Uchiyama, Takashi
AU  - Uchiyama T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HLA-B Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptides)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (CDKL5 protein, human)
SB  - IM
MH  - Antigens, Neoplasm/chemistry/*immunology
MH  - B-Lymphocytes
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Cell Line, Tumor
MH  - Chromatography, Liquid
MH  - Cytotoxicity, Immunologic
MH  - Dendritic Cells/immunology
MH  - HLA-B Antigens/immunology
MH  - Herpesvirus 4, Human
MH  - Histocompatibility Antigens Class I/chemistry/*immunology
MH  - Humans
MH  - Immunotherapy
MH  - Leukemia-Lymphoma, Adult T-Cell/*immunology/therapy
MH  - Mass Spectrometry
MH  - Oligopeptides/immunology
MH  - Peptides/*analysis/immunology/metabolism
MH  - Protein Serine-Threonine Kinases/chemistry/*immunology
EDAT- 2007/06/26 09:00
MHDA- 2007/08/19 09:00
CRDT- 2007/06/26 09:00
PHST- 2007/06/26 09:00 [pubmed]
PHST- 2007/08/19 09:00 [medline]
PHST- 2007/06/26 09:00 [entrez]
AID - 00002371-200707000-00004 [pii]
AID - 10.1097/CJI.0b013e3180336771 [doi]
PST - ppublish
SO  - J Immunother. 2007 Jul-Aug;30(5):499-505. doi: 10.1097/CJI.0b013e3180336771.