title: Identification of the H2-Kd-restricted cytotoxic T lymphocyte epitopes of a tumor-associated antigen, SPARC, which can stimulate antitumor immunity without causing autoimmune disease in mice.
abstract: We previously reported that the secreted protein acidic and rich in cystein (SPARC) was overexpressed in melanoma in humans, and the serum SPARC level was useful as a novel tumor marker for melanoma. SPARC was also reported to be overexpressed in various human cancers. In this study, we asked whether SPARC-specific cytotoxic T lymphocytes (CTL) could induce antitumor immunity to SPARC-expressing tumor in mice or not as a preclinical study of SPARC-directed anticancer immunotherapy. Because of similarities in the structural motifs of major histocompatibility complex-binding peptides between H2-Kd and HLA-A24 (A*2402), the most common human leukocyte antigen class I allele in the Japanese population, we attempted to identify the H2-Kd-restricted SPARC epitope for CTL in BALB/c mice and we found that the mouse SPARC143-151 (DYIGPCKYI) and SPARC225-234 (MYIFPVHWQF) peptides could induce peptide-reactive CTL in BALB/c mice without causing autoimmune diseases. The immunization of mice with SPARC225-234 peptide-pulsed bone marrow-derived dendritic cells (BMDC) inhibited the growth of s.c. inoculated mouse mammary cancer cell line, N2C, expressing SPARC and these mice lived longer than the mice immunized with peptide-unpulsed BMDC. In conclusion, our study indicated that SPARC peptide-based cancer immunotherapy was effective and safe at least in a mouse tumor prevention model.
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honju, Kumamoto 860-8556, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ikuta
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hayashida
authors.forename: Shinya
authors.initials: S
authors.lastname: Hirata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Irie
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
authors.forename: Tatsuko
authors.initials: T
authors.lastname: Kubo
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
authors.forename: Mikio
authors.initials: M
authors.lastname: Monji
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D015676:Osteonectin / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D015676:Osteonectin; D010446:Peptide Fragments; D012333:RNA, Messenger