title: WT1 peptide vaccination combined with BCG-CWS is more efficient for tumor eradication than WT1 peptide vaccination alone.
abstract: A Wilms' tumor gene WT1 is expressed at high levels not only in most types of leukemia but also in various types of solid tumors, including lung and breast cancer. WT1 protein has been reported to serve as a target antigen for tumor-specific immunotherapy both in vitro in human systems and in vivo in murine models. We have shown that mice immunized with WT1 peptide or WT1 cDNA could reject a challenge from WT1-expressing tumor cells (a "prophylactic" model). However, it was not examined whether WT1 peptide vaccination had the potency to reject tumor cells in a "therapeutic" setting. In the present study, we demonstrated for the first time that WT1 peptide vaccination combined with Mycobacterium bovis bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) was more effective for eradication of WT1-expressing tumor cells that had been implanted into mice before vaccination (a "therapeutic" model) compared with WT1 peptide vaccination alone. An intradermal injection of BCG-CWS into mice, followed by that of WT1 peptide at the same site on the next day, generated WT1-specific cytotoxic T lymphocytes (CTLs) and led to rejection of WT1-expressing leukemia or lung cancer cells. These results showed that BCG-CWS, which was well known to enhance innate immunity, could enhance WT1-specific immune responses (acquired immunity) in combination with WT1 peptide vaccination. Therefore, WT1 peptide vaccination combined with BCG-CWS may be applied to cancer immunotherapy in clinical settings.
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, 1-7 Yamada-Oka, Suita City, 565-0871 Osaka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakajima
authors.forename: Kotomi
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawakami
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikegame
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hoshida
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Fujiki
authors.forename: Akiko
authors.initials: A
authors.lastname: Nakano
authors.forename: Tomoki
authors.initials: T
authors.lastname: Masuda
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.forename: Yuki
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Olga A
authors.initials: OA
authors.lastname: Elisseeva
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ogawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Azuma
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Aozasa
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003114:Colony-Forming Units Assay; D007167:Immunotherapy; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007938:Leukemia / Q000378:metabolism / Q000628:therapy*; D008070:Lipopolysaccharides / Q000276:immunology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology* / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000637:transplantation; D014611:Vaccination; D025721:WT1 Proteins / Q000276:immunology* / Q000627:therapeutic use
chemical_list: C042138:BCG lipopolysaccharide; D019496:Cancer Vaccines; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D025721:WT1 Proteins