WT1 peptide vaccination combined with BCG-CWS is more efficient for tumor eradication than WT1 peptide vaccination alone.
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.
Nakajima
Hiroko
H
Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, 1-7 Yamada-Oka, Suita City, 565-0871 Osaka, Japan.
Kawasaki
Kotomi
K
Oka
Yoshihiro
Y
Tsuboi
Akihiro
A
Kawakami
Manabu
M
Ikegame
Kazuhiro
K
Hoshida
Yoshihiko
Y
Fujiki
Fumihiro
F
Nakano
Akiko
A
Masuda
Tomoki
T
Wu
Fei
F
Taniguchi
Yuki
Y
Yoshihara
Satoshi
S
Elisseeva
Olga A
OA
Oji
Yusuke
Y
Ogawa
Hiroyasu
H
Azuma
Ichiro
I
Kawase
Ichiro
I
Aozasa
Katsuyuki
K
Sugiyama
Haruo
H
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
C042138:BCG lipopolysaccharide; D019496:Cancer Vaccines; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D025721:WT1 Proteins