title: DNA vaccination of HSP105 leads to tumor rejection of colorectal cancer and melanoma in mice through activation of both CD4 T cells and CD8 T cells.
abstract: We report that HSP105, identified by serological identification of antigens by recombinant expression cloning (SEREX), is overexpressed in a variety of human cancers, including colorectal, pancreatic, thyroid, esophageal, and breast carcinoma, but is not expressed in normal tissues except for the testis. The amino acid sequences and expression patterns of HSP105 are very similar in humans and mice. In this study, we set up a preclinical study to investigate the usefulness of a DNA vaccine producing mouse HSP105 whole protein for cancer immunotherapy in vivo using BALB/c and C57BL/6 mice, Colon26, a syngeneic endogenously HSP105-expressing colorectal cancer cell line, and B16.F10, a melanoma cell line. The DNA vaccine was used to stimulate HSP105-specific T-cell responses. Fifty percent of mice immunized with the HSP105 DNA vaccine completely suppressed the growth of subcutaneous Colon26 or B16.F10 cells accompanied by massive infiltration of both CD4+ T cells and CD8+ T cells into tumors. In cell transfer or depletion experiments we proved that both CD4+ T cells and CD8+ T cells induced by these vaccines play critical roles in the activation of antitumor immunity. Evidence of autoimmune reactions was not present in surviving mice that had rejected tumor cell challenges. We found that HSP105 was highly immunogenic in mice and that the HSP105 DNA vaccination induced antitumor immunity without causing autoimmunity. Therefore, HSP105 is an ideal tumor antigen that could be useful for immunotherapy or the prevention of various human tumors that overexpress HSP105, including colorectal cancer and melanoma.
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Hongo, Kumamoto 860-8556, Japan. mxnishim@gpo.kumamoto-u.ac.jp
authors.forename: Masafumi
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yokomine
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
authors.forename: Mikio
authors.initials: M
authors.lastname: Monji
authors.forename: Seiji
authors.initials: S
authors.lastname: Hosaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Komori
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoshitake
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Motomura
authors.forename: Motozumi
authors.initials: M
authors.lastname: Minohara
authors.forename: Tatsuko
authors.initials: T
authors.lastname: Kubo
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ishihara
authors.forename: Takumi
authors.initials: T
authors.lastname: Hatayama
authors.forename: Michio
authors.initials: M
authors.lastname: Ogawa
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D050957:HSP110 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D007167:Immunotherapy / Q000379:methods; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D012878:Skin Neoplasms / Q000473:pathology*; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D050957:HSP110 Heat-Shock Proteins; D019444:Vaccines, DNA