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Identification of SPARC as a candidate target antigen for immunotherapy of various cancers
Author(s) -
Inoue Mitsuhiro,
Senju Satoru,
Hirata Shinya,
Ikuta Yoshiaki,
Hayashida Yuki,
Irie Atsushi,
Harao Michiko,
Imai Katsunori,
Tomita Yusuke,
Tsunoda Takuya,
Furukawa Yoichi,
Ito Takaaki,
Nakamura Yusuke,
Baba Hideo,
Nishimura Yasuharu
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25160
Subject(s) - epitope , ctl* , cancer immunotherapy , cancer research , antigen , cytotoxic t cell , immunotherapy , cancer , immune system , biology , peripheral blood mononuclear cell , immunology , cd8 , in vitro , biochemistry , genetics
To establish efficient anticancer immunotherary, it is important to identify tumor‐associated antigens (TAAs) directing the immune system to attack cancer. A genome‐wide cDNA microarray analysis identified that secreted protein acidic and rich in cysteine ( SPARC ) gene is overexpressed in the gastric, pancreatic and colorectal cancer tissues but not in their noncancerous counterparts. This study attempted to identify HLA‐A24 ( A*2402 )‐restricted and SPARC‐derived CTL epitopes. We previously identified H‐2K d ‐restricted and SPARC‐derived CTL epitope peptides in BALB/c mice, of which H‐2K d ‐binding peptide motif is comparable with that of HLA‐A24 binding peptides. By using these peptides, we tried to induce HLA‐A24 ( A*2402 )‐restricted and SPARC‐reactive human CTLs and demonstrated an antitumor immune response. The SPARC‐A24‐1 143–151 (DYIGPCKYI) and SPARC‐A24‐4 225–234 (MYIFPVHWQF) peptides‐reactive CTLs were successfully induced from peripheral blood mononuclear cells by in vitro stimulation with these two peptides in HLA‐A24 ( A*2402 ) positive healthy donors and cancer patients, and these CTLs exhibited cytotoxicity specific to cancer cells expressing both SPARC and HLA‐A24 ( A*2402 ). Furthermore, the adoptive transfer of the SPARC‐specific CTLs could inhibit the tumor growth in nonobese diabetic/severe combined immunodeficient mice bearing human cancer cells expressing both HLA‐A24 ( A*2402 ) and SPARC. These findings suggest that SPARC is a potentially useful target candidate for cancer immunotherapy.