The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     
 


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Oka, Y.
Right arrow Articles by Sugiyama, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oka, Y.
Right arrow Articles by Sugiyama, H.
The Journal of Immunology, 2000, 164: 1873-1880.
Copyright © 2000 by The American Association of Immunologists

Cancer Immunotherapy Targeting Wilms’ Tumor Gene WT1 Product1

Yoshihiro Oka2,*, Keiko Udaka2, Akihiro Tsuboi*, Olga A. Elisseeva*, Hiroyasu Ogawa*, Katsuyuki Aozasa{dagger}, Tadamitsu Kishimoto and Haruo Sugiyama3,{ddagger}

Departments of * Molecular Medicine, {dagger} Pathology, and {ddagger} Clinical Laboratory Science, Osaka University Medical School, Suita, Osaka, Japan; § RESTO, JST, and Department of Biophysics, Kyoto University, Sakyo, Kyoto, Japan; and Osaka University, Osaka, Japan

The Wilms’ tumor gene WT1 is expressed at high levels not only in acute myelocytic and lymphocytic leukemia and in chronic myelocytic leukemia but also in various types of solid tumors including lung cancers. To determine whether the WT1 protein can serve as a target Ag for tumor-specific immunity, three 9-mer WT1 peptides (Db126, Db221, and Db235), which contain H-2Db-binding anchor motifs and have a comparatively higher binding affinity for H-2Db molecules, were tested in mice (C57BL/6, H-2Db) for in vivo induction of CTLs directed against these WT1 peptides. Only one peptide, Db126, with the highest binding affinity for H-2Db molecules induced vigorous CTL responses. The CTLs specifically lysed not only Db126-pulsed target cells dependently upon Db126 concentrations but also WT1-expressing tumor cells in an H-2Db-restricted manner. The sensitizing activity to the Db126-specific CTLs was recovered from the cell extract of WT1-expressing tumor cells targeted by the CTLs in the same retention time as that needed for the synthetic Db126 peptide in RP-HPLC, indicating that the Db126-specific CTLs recognize the Db126 peptide to kill WT1-expressing target cells. Furthermore, mice immunized with the Db126 peptide rejected challenges by WT1-expressing tumor cells and survived for a long time with no signs of autoaggression by the CTLs. Thus, the WT1 protein was identified as a novel tumor Ag. Immunotherapy targeting the WT1 protein should find clinical application for various types of human cancers.




This article has been cited by other articles:


Home page
Clin. Cancer Res.Home page
T. Osada, C. Y. Woo, M. McKinney, X. Y. Yang, G. Lei, H. G. LaBreche, Z. C. Hartman, D. Niedzwiecki, N. Chao, A. Amalfitano, et al.
Induction of Wilms' Tumor Protein (WT1)-Specific Antitumor Immunity Using a Truncated WT1-Expressing Adenovirus Vaccine
Clin. Cancer Res., April 15, 2009; 15(8): 2789 - 2796.
[Abstract] [Full Text] [PDF]


Home page
The OncologistHome page
E. L.J.M. Smits, Z. N. Berneman, and V. F.I. Van Tendeloo
Immunotherapy of Acute Myeloid Leukemia: Current Approaches
Oncologist, March 1, 2009; 14(3): 240 - 252.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
C. Chaise, S. L. Buchan, J. Rice, J. Marquet, H. Rouard, M. Kuentz, G. E. Vittes, V. Molinier-Frenkel, J.-P. Farcet, H. J. Stauss, et al.
DNA vaccination induces WT1-specific T-cell responses with potential clinical relevance
Blood, October 1, 2008; 112(7): 2956 - 2964.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
K. Rezvani, A. S. M. Yong, B. N. Savani, S. Mielke, K. Keyvanfar, E. Gostick, D. A. Price, D. C. Douek, and A. J. Barrett
Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia
Blood, September 15, 2007; 110(6): 1924 - 1932.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
K. Rezvani, J. M. Brenchley, D. A. Price, Y. Kilical, E. Gostick, A. K. Sewell, J. Li, S. Mielke, D. C. Douek, and A. J. Barrett
T-Cell Responses Directed against Multiple HLA-A*0201-Restricted Epitopes Derived from Wilms' Tumor 1 Protein in Patients with Leukemia and Healthy Donors: Identification, Quantification, and Characterization
Clin. Cancer Res., December 15, 2005; 11(24): 8799 - 8807.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
E. S. Doubrovina, M. M. Doubrovin, S. Lee, J.-H. Shieh, G. Heller, E. Pamer, and R. J. O'Reilly
In vitro Stimulation with WT1 Peptide-Loaded Epstein-Barr Virus-Positive B Cells Elicits High Frequencies of WT1 Peptide-Specific T Cells with In vitro and In vivo Tumoricidal Activity
Clin. Cancer Res., November 1, 2004; 10(21): 7207 - 7219.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
Y. Oka, A. Tsuboi, T. Taguchi, T. Osaki, T. Kyo, H. Nakajima, O. A. Elisseeva, Y. Oji, M. Kawakami, K. Ikegame, et al.
Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression
PNAS, September 21, 2004; 101(38): 13885 - 13890.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
T. Tsukahara, Y. Nabeta, S. Kawaguchi, H. Ikeda, Y. Sato, K. Shimozawa, K. Ida, H. Asanuma, Y. Hirohashi, T. Torigoe, et al.
Identification of Human Autologous Cytotoxic T-Lymphocyte-Defined Osteosarcoma Gene That Encodes a Transcriptional Regulator, Papillomavirus Binding Factor
Cancer Res., August 1, 2004; 64(15): 5442 - 5448.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
J. A. Alberta, G. M. Springett, H. Rayburn, T. A. Natoli, J. Loring, J. A. Kreidberg, and D. Housman
Role of the WT1 tumor suppressor in murine hematopoiesis
Blood, April 1, 2003; 101(7): 2570 - 2574.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
C. Scheibenbogen, A. Letsch, E. Thiel, A. Schmittel, V. Mailaender, S. Baerwolf, D. Nagorsen, and U. Keilholz
CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia
Blood, August 28, 2002; 100(6): 2132 - 2137.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
M. Makita, A. Hiraki, T. Azuma, A. Tsuboi, Y. Oka, H. Sugiyama, S. Fujita, M. Tanimoto, M. Harada, and M. Yasukawa
Antilung Cancer Effect of WT1-specific Cytotoxic T Lymphocytes
Clin. Cancer Res., August 1, 2002; 8(8): 2626 - 2631.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
O. A. Elisseeva, Y. Oka, A. Tsuboi, K. Ogata, F. Wu, E. H. Kim, T. Soma, H. Tamaki, M. Kawakami, Y. Oji, et al.
Humoral immune responses against Wilms tumor gene WT1 product in patients with hematopoietic malignancies
Blood, May 1, 2002; 99(9): 3272 - 3279.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Gaiger, V. Reese, M. L. Disis, and M. A. Cheever
Immunity to WT1 in the animal model and in patients with acute myeloid leukemia
Blood, August 15, 2000; 96(4): 1480 - 1489.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2000 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2000 by The American Association of Immunologists, Inc. All rights reserved.