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: Hiroko Nakajima, Kotomi Kawasaki, Yoshihiro Oka, Akihiro Tsuboi, Manabu Kawakami, Kazuhiro Ikegame, Yoshihiko Hoshida, Fumihiro Fujiki, Akiko Nakano, Tomoki Masuda, Fei Wu, Yuki Taniguchi, Satoshi Yoshihara, Olga A Elisseeva, Yusuke Oji, Hiroyasu Ogawa, Ichiro Azuma, Ichiro Kawase, Katsuyuki Aozasa, Haruo Sugiyama
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 53 Issue 7 Pg. 617-24 (Jul 2004) ISSN: 0340-7004 [Print] Germany
• PMID: 15175906 (Publication Type: Journal Article)
• Copyright: Copyright 2004 Springer-Verlag

Chemical References

• BCG lipopolysaccharide
• Cancer Vaccines
• Lipopolysaccharides
• Peptide Fragments
• WT1 Proteins

Topics

• Animals
• Bone Marrow (immunology, metabolism, pathology)
• Cancer Vaccines (therapeutic use)
• Colony-Forming Units Assay
• Immunotherapy
• Kidney (immunology, metabolism, pathology)
• Leukemia (metabolism, therapy)
• Lipopolysaccharides (immunology)
• Lung Neoplasms (metabolism, therapy)
• Male
• Mice
• Mice, Inbred C57BL
• Peptide Fragments (immunology, therapeutic use)
• T-Lymphocytes, Cytotoxic (immunology)
• Tumor Cells, Cultured (transplantation)
• Vaccination
• WT1 Proteins (immunology, therapeutic use)