Open AccessIdentification of human leukocyte antigen‐A24‐restricted epitope peptides derived from gene products upregulated in lung and esophageal cancers as novel targets for immunotherapy
Author(s) -
Suda Takako,
Tsunoda Takuya,
Daigo Yataro,
Nakamura Yusuke,
Tahara Hideaki
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00603.x
Subject(s) - ctl* , cytotoxic t cell , epitope , antigen , human leukocyte antigen , immunology , biology , cancer immunotherapy , mhc class i , cancer research , immune system , immunotherapy , major histocompatibility complex , cd8 , biochemistry , in vitro
For the development of cancer vaccine therapies, we have searched for possible epitope peptides that can elicit cytotoxic T lymphocytes (CTL) to the TTK protein kinase ( TTK ), lymphocyte antigen 6 complex locus K ( LY6K ) and insulin‐like growth factor (IGF)‐II mRNA binding protein 3 ( IMP‐3 ), which were previously identified to be transactivated in the majority of lung and esophageal cancers. We screened 31, 17 and 17 candidate human leukocyte antigen (HLA)‐A*2402‐binding peptides to parts of TTK , LY6K and IMP‐3 , respectively. As a result, we successfully established strong CTL clones stimulated by TTK‐567 (SYRNEIAYL), LY6K‐177 (RYCNLEGPPI) and IMP‐3‐508 (KTVNELQNL) that have specific cytotoxic activities against the HLA‐A24‐positive target cells pulsed with the candidate peptides. Subsequent analysis of the CTL clones also revealed their cytotoxic activities against lung and esophageal tumor cells that endogenously express TTK, LY6K or IMP‐3. A cold target inhibition assay further confirmed that the CTL cell clones specifically recognized the MHC class I–peptide complex. Our results strongly imply that TTK, LY6K and IMP‐3 are novel tumor‐associated antigens recognized by CTL, and TTK‐567 (SYRNEIAYL), LY6K‐177 (RYCNLEGPPI) and IMP‐3‐508 (KTVNELQNL) are HLA‐A24‐restricted epitope peptides that can induce potent and specific immune responses against lung and esophageal cancer cells expressing TTK, LY6K and IMP‐3. ( Cancer Sci 2007; 98: 1803–1808)