WT1 peptide vaccination combined with BCG-CWS is more efficient for tumor eradication than WT1 peptide vaccination alone

• Published in: Cancer Immunology, Immunotherapy Vol. 53; no. 7; pp. 617 - 624
• Main Authors: NAKAJIMA, Hiroko, KAWASAKI, Kotomi, FEI WU, TANIGUCHI, Yuki, YOSHIHARA, Satoshi, ELISSEEVA, Olga A, OJI, Yusuke, OGAWA, Hiroyasu, AZUMA, Ichiro, KAWASE, Ichiro, AOZASA, Katsuyuki, SUGIYAMA, Haruo, OKA, Yoshihiro, TSUBOI, Akihiro, KAWAKAMI, Manabu, IKEGAME, Kazuhiro, HOSHIDA, Yoshihiko, FUJIKI, Fumihiro, NAKANO, Akiko, MASUDA, Tomoki
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.07.2004; Springer Nature B.V; Springer-Verlag
• Subjects: Animals; Antigens; Antineoplastic agents; Biological and medical sciences; Bone Marrow - immunology; Bone Marrow - metabolism; Bone Marrow - pathology; Breast cancer; Cancer Vaccines - therapeutic use; Colony-Forming Units Assay; Immunotherapy; Kidney - immunology; Kidney - metabolism; Kidney - pathology; Leukemia; Leukemia - metabolism; Leukemia - therapy; Lipopolysaccharides - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - therapy; Male; Medical sciences; Medicine; Mice; Mice, Inbred C57BL; Mycobacterium bovis; Original; Peptide Fragments - immunology; Peptide Fragments - therapeutic use; Peptides; Pharmacology. Drug treatments; Proteins; T-Lymphocytes, Cytotoxic - immunology; Tumor Cells, Cultured - transplantation; Tumors; University graduates; Vaccination; WT1 Proteins - immunology; WT1 Proteins - therapeutic use; United States > US; Japan; Peptides; Vaccination; BCG; Wilms tumor gene; Malignant tumor; Eradication; Prevention; Wilms' tumor gene; Treatment; BCG-CWS; WT1; Immunotherapy; Tumor suppressor gene
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-003-0498-0

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.