title: Identification of SPARC as a candidate target antigen for immunotherapy of various cancers.
abstract: 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.
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Inoue
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
authors.forename: Shinya
authors.initials: S
authors.lastname: Hirata
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ikuta
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hayashida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Irie
authors.forename: Michiko
authors.initials: M
authors.lastname: Harao
authors.forename: Katsunori
authors.initials: K
authors.lastname: Imai
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tomita
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ito
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016219:Immunotherapy, Adoptive; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D020411:Oligonucleotide Array Sequence Analysis; D015676:Osteonectin / Q000737:chemistry / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D017931:DNA Primers; D015676:Osteonectin