The Experts below are selected from a list of 15162 Experts worldwide ranked by ideXlab platform
Akihiro Tsuboi - One of the best experts on this subject based on the ideXlab platform.
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Two distinct effector memory cell populations of WT1 (Wilms’ Tumor Gene 1)-specific cytotoxic T lymphocytes in acute myeloid leukemia patients
Cancer Immunology Immunotherapy, 2015Co-Authors: Yoshiki Nakae, Hiroko Nakajima, Naoki Hosen, Sumiyuki Nishida, Satoshi Takashima, Fumihiro Fujiki, Soyoko Morimoto, Toshio Kamiya, Jun Nakata, Akihiro TsuboiAbstract:Wilms’ Tumor Gene 1 (WT1) protein is a promising Tumor-associated antigen for cancer immunotherapy. We have been performing WT1 peptide vaccination with good clinical responses in over 750 patients with leukemia or solid cancers. In this study, we Generated single-cell Gene-expression profiles of the effector memory (EM) subset of WT1-specific cytotoxic T lymphocytes (CTLs) in peripheral blood of nine acute myeloid leukemia patients treated with WT1 peptide vaccine, in order to discriminate responders ( WT1 mRNA levels in peripheral blood decreased to undetectable levels, decreased but stayed at abnormal levels, were stable at undetectable levels, or remained unchanged from the initial abnormal levels more than 6 months after WT1 vaccination) from non-responders (leukemic blast cells and/or WT1 mRNA levels increased relative to the initial state within 6 months of WT1 vaccination) prior to WT1 vaccination. Cluster and principal component analyses performed using 83 Genes did not discriminate between responders and non-responders prior to WT1 vaccination. However, these analyses revealed that EM subset of WT1-specific CTLs could be divided into two groups: the “activated” and “quiescent” states; in responders, EM subset of the CTLs shifted to the “quiescent” state, whereas in non-responders, those shifted to the “activated” state following WT1 vaccination. These results demonstrate for the first time the existence of two distinct EM states, each of which was characteristic of responders or non-responders, of WT1-specific CTLs in AML patients, and raises the possibility of using advanced Gene-expression profile analysis to clearly discriminate between responders and non-responders prior to WT1 vaccination.
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Tumor immunotherapy targeting WT1 (Wilms’ Tumor Gene) peptide for bone and soft-tissue sarcomas: A preliminary report
Journal of Clinical Oncology, 2007Co-Authors: Takafumi Ueda, Akihiro Tsuboi, Shigeki Kakunaga, Nobuyuki Hashimoto, Akira Myoui, Katsuyuki Aozasa, Haruo Sugiyama, Hideki YoshikawaAbstract:10042 Background: WT1 (Wilms’ Tumor Gene) is originally isolated as a Tumor-suppressor Gene in a subset of Wilms’ Tumors, however, recent studies have indicated its oncogenic activity in various ty...
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The Wilms' Tumor Gene WT1 is a common marker of progenitor cells in fetal liver
Biochemical and Biophysical Research Communications, 2005Co-Authors: Keisuke Kanato, Manabu Kawakami, Akihiro Tsuboi, Naoki Hosen, Toshiaki Shirakata, Sumiyuki Nishida, Masashi Yanagihara, Naomi Nakagata, Tsutomu Nakazawa, Tomoki MasudaAbstract:Abstract It is well known that the Wilms’ Tumor Gene WT1 plays an important role in cell proliferation and differentiation, and in organ development. In this study, to examine the role of the WT1 Gene in lineage determination, fetal liver cells from LacZ-transgenic mice, in which WT1 expression was marked by the expression of the LacZ Gene driven by WT1 promoter, were FACS-sorted according to LacZ expression of high (LacZ++) or undetectable (LacZ−) levels, which paralleled endogenous WT1 expression levels. LacZ++ fetal liver cells were enriched by hepatocyte and endothelial progenitor cells. These results indicated that WT1 expression is a common marker of both hepatocyte and endothelial progenitors. These results also implied a role of the WT1 Gene in lineage determination.
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Induction of WT1 (Wilms' Tumor Gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression.
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Yoshihiro Oka, Taiichi Kyo, Hiroko Nakajima, Olga A Elisseeva, Manabu Kawakami, Yusuke Oji, Tetsuya Taguchi, Akihiro Tsuboi, Tadashi Osaki, Kazuhiro IkegameAbstract:The Wilms' Tumor Gene WT1 is overexpressed in leukemias and various types of solid Tumors, and the WT1 protein was demonstrated to be an attractive target antigen for immunotherapy against these malignancies. Here, we report the outcome of a phase I clinical study of WT1 peptide-based immunotherapy for patients with breast or lung cancer, myelodysplastic syndrome, or acute myeloid leukemia. Patients were intradermally injected with an HLA-A*2402-restricted, natural, or modified 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant at 0.3, 1.0, or 3.0 mg per body at 2-week intervals, with toxicity and clinical and immunological responses as the principal endpoints. Twenty-six patients received one or more WT1 vaccinations, and 18 of the 26 patients completed WT1 vaccination protocol with three or more injections of WT1 peptides. Toxicity consisted only of local erythema at the WT1 vaccine injection sites in patients with breast or lung cancer or acute myeloid leukemia with adequate normal hematopoiesis, whereas severe leukocytopenia occurred in patients with myelodysplastic syndrome with abnormal hematopoiesis derived from WT1-expressing, transformed hematopoietic stem cells. Twelve of the 20 patients for whom the efficacy of WT1 vaccination could be assessed showed clinical responses such as reduction in leukemic blast cells or Tumor sizes and/or Tumor markers. A clear correlation was observed between an increase in the frequencies of WT1-specific cytotoxic T lymphocytes after WT1 vaccination and clinical responses. It was therefore demonstrated that WT1 vaccination could induce WT1-specific cytotoxic T lymphocytes and result in cancer regression without damage to normal tissues.
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Cytotoxic T-Lymphocyte Responses Elicited to Wilms' Tumor Gene WT1 Product by DNA Vaccination
Journal of Clinical Immunology, 2000Co-Authors: Akihiro Tsuboi, Olga A Elisseeva, Yoshihiro Oka, Hiroyasu Ogawa, Katsuyuki Aozasa, Keiko Udaka, Tadamitsu Kishimoto, Hanfen Li, Kotomi Kawasaki, Haruo SugiyamaAbstract:We recently have reported that Wilms' Tumor Gene WT1 is highly expressed not only in leukemias but also in various types of solid Tumors and that WT1 protein is a novel Tumor antigen against which cytotoxic T lymphocytes (CTLs) can be elicited by immunization with 9-mer WT1 peptides capable of binding to major histocompatibility complex (MHC) class I molecules. In the present study, plasmid DNA encoding murine full-length WT1 protein was injected intramuscularly into C57BL/6 mice. The mice vaccinated with the WT1 plasmid DNA elicited CTLs against the WT1 protein, and the CTLs specifically killed WT1-expressing Tumor cells in a MHC class I-restricted manner. Furthermore, the vaccinated mice rejected the challenges of WT1-expressing Tumor cells and survived with no signs of autoimmunity caused by the CTLs. These results demonstrated that vaccination with the WT1 plasmid DNA can elicit CTL responses specific for the WT1 protein, resulting in the acquisition of rejection activity against challenges of WT1-expressing Tumor cells. This WT1 DNA vaccination may find clinical application for various types of solid Tumors as well as leukemias.
Haruo Sugiyama - One of the best experts on this subject based on the ideXlab platform.
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Cancer immunotherapy targeting Wilms' Tumor Gene WT1 product.
Expert Review of Vaccines, 2020Co-Authors: Haruo SugiyamaAbstract:The Wilms’ Tumor Gene WT1 is expressed at high levels in leukemic blast cells in most acute myeloid and lymphoblastic leukemias. In myelodysplastic syndrome, WT1 mRNA expression levels increase along with disease progression; thus, WT1 mRNA is a Tumor marker for leukemic blast cells. WT mRNA is also expressed at high levels in various types of solid cancers, including cancers of the lung, breast, colon and pancreas. Patients with WT1-expressing Tumors produce antibodies and cytotoxic T-lymphocytes against WT1 protein, indicating that WT1 protein is highly immunogenic and a promising Tumor antigen. Major histocompatibility complex class I-restricted cytotoxic T-lymphocyte and class II-restricted helper epitopes of WT1 protein were identified, and clinical studies of cancer immunotherapy using these cytotoxic T-lymphocyte epitope peptides were performed without significant adverse effect and with clinical results promising enough to encourage further clinical trials. The clinical efficacy of cancer immunoth...
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WT1 (Wilms' Tumor Gene 1) : biology and cancer immunotherapy
Japanese Journal of Clinical Oncology, 2010Co-Authors: Haruo SugiyamaAbstract:: Wilms' Tumor Gene WT1 encodes a transcription factor and plays an important role in cell growth and differentiation. The WT1 Gene is highly expressed in leukemia and various types of solid Tumors, whereas WT1 is a Tumor marker convenient for the detection of minimal residual disease of leukemia. The WT1 Gene was originally defined as a Tumor suppressor Gene, but we proposed that it was, on the contrary, an oncoGene. Furthermore, the WT1 protein has proven to be a promising Tumor-associated antigen, in which many human leukocyte antigen class I- or II-restricted WT1 epitopes have been identified. Clinical trials of WT1-targeted immunotherapy have confirmed its safety and clinical efficacy. WT1-specific cytotoxic T lymphocytes and WT1 antibodies are spontaneously induced in Tumor-bearing patients, probably because of high immunogenicity of the WT1 protein. WT1-specific cytotoxic T lymphocytes make a major contribution to the graft-versus-leukemia effect after allogenic stem cell transplantation. When 75 cancer antigens including WT1 were prioritized according to several criteria such as therapeutic function and immunogenicity, WT1 was ranked as the top antigen. These findings suggest that a new era of WT1 immunotherapy is imminent.
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Tumor immunotherapy targeting WT1 (Wilms’ Tumor Gene) peptide for bone and soft-tissue sarcomas: A preliminary report
Journal of Clinical Oncology, 2007Co-Authors: Takafumi Ueda, Akihiro Tsuboi, Shigeki Kakunaga, Nobuyuki Hashimoto, Akira Myoui, Katsuyuki Aozasa, Haruo Sugiyama, Hideki YoshikawaAbstract:10042 Background: WT1 (Wilms’ Tumor Gene) is originally isolated as a Tumor-suppressor Gene in a subset of Wilms’ Tumors, however, recent studies have indicated its oncogenic activity in various ty...
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The Wilms’ Tumor Gene WT1 Is Over-Expressed in Immature Leukemia Cells but Not Necessary for Leukemia Development in Mouse Leukemia Models.
Blood, 2006Co-Authors: Naoki Hosen, Haruo Sugiyama, Irving L. WeissmanAbstract:The Wilms Tumor Gene WT1, which is over-expressed in almost all leukemia, is one of the most promising targets for immunotherapy. To clarify which cells express WT1, we Generated a knock-in reporter GFP mice (WT1 GFP/+) and assayed for WT1 expression in normal and leukemic hematopoietic cells. In normal hematopoietic cells, WT1 was expressed in none of the long-term hematopoietic stem cells (HSCs) and very few (
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Cytotoxic T-Lymphocyte Responses Elicited to Wilms' Tumor Gene WT1 Product by DNA Vaccination
Journal of Clinical Immunology, 2000Co-Authors: Akihiro Tsuboi, Olga A Elisseeva, Yoshihiro Oka, Hiroyasu Ogawa, Katsuyuki Aozasa, Keiko Udaka, Tadamitsu Kishimoto, Hanfen Li, Kotomi Kawasaki, Haruo SugiyamaAbstract:We recently have reported that Wilms' Tumor Gene WT1 is highly expressed not only in leukemias but also in various types of solid Tumors and that WT1 protein is a novel Tumor antigen against which cytotoxic T lymphocytes (CTLs) can be elicited by immunization with 9-mer WT1 peptides capable of binding to major histocompatibility complex (MHC) class I molecules. In the present study, plasmid DNA encoding murine full-length WT1 protein was injected intramuscularly into C57BL/6 mice. The mice vaccinated with the WT1 plasmid DNA elicited CTLs against the WT1 protein, and the CTLs specifically killed WT1-expressing Tumor cells in a MHC class I-restricted manner. Furthermore, the vaccinated mice rejected the challenges of WT1-expressing Tumor cells and survived with no signs of autoimmunity caused by the CTLs. These results demonstrated that vaccination with the WT1 plasmid DNA can elicit CTL responses specific for the WT1 protein, resulting in the acquisition of rejection activity against challenges of WT1-expressing Tumor cells. This WT1 DNA vaccination may find clinical application for various types of solid Tumors as well as leukemias.
Eckhard Thiel - One of the best experts on this subject based on the ideXlab platform.
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a clinical and immunologic phase 2 trial of wilms Tumor Gene product 1 wt1 peptide vaccination in patients with aml and mds
Blood, 2009Co-Authors: Ulrich Keilholz, Eckhard Thiel, Anne Letsch, Antonia Busse, Anne Marie Asemissen, Sandra Bauer, Igor Wolfgang Blau, Wolfkarsten Hofmann, Lutz Uharek, Carmen ScheibenbogenAbstract:This study investigated the immunogenicity of Wilms Tumor Gene product 1 (WT1)–peptide vaccination in WT1-expressing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients without curative treatment option. Vaccination consisted of granulocyte-macrophage colony-stimulating factor subcutaneously days 1 to 4, and WT1.126-134 peptide and 1 mg keyhole limpet hemocyanin on day 3. The initial 9 patients received 4 vaccinations biweekly, then monthly, and the subsequent 10 patients received continual biweekly vaccination. Seventeen AML patients and 2 refractory anemia with excess blasts patients received a median of 11 vaccinations. Treatment was well tolerated. Objective responses in AML patients were 10 stable diseases (SDs) including 4 SDs with more than 50% blast reduction and 2 with hematologic improvement. An additional 4 patients had clinical benefit after initial progression, including 1 complete remission and 3 SDs. WT1 mRNA levels decreased at least 3-fold from baseline in 35% of patients. In 8 of 18 patients, WT1-tetramer+ T cells increased in blood and in 8 of 17 patients in bone marrow, with a median frequency in bone marrow of 0.18% at baseline and 0.41% in week 18. This WT1 vaccination study provides immunologic, molecular, and preliminary evidence of potential clinical efficacy in AML patients, warranting further investigations.
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Wilms Tumor Gene (WT1) Expression as a Panleukemic Marker
International Journal of Hematology, 2002Co-Authors: Hans D. Menssen, Jan M. Siehl, Eckhard ThielAbstract:The Wilms Tumor Gene ( WT1 ) is expressed in blasts of patients with acute leukemia, irrespective of lineage, and WT1 nuclear protein is detectable in the majority of such blasts. Only very few physiologic hematopoietic progenitors express WT1 , but the WT1 expression level of these progenitors and that of leukemic blasts are comparable. Although not specific for acute hematologic malignant diseases, continuous WT1 expression in almost all leukemic blasts strikingly contrasts to its rather transient expression in very few physiologic hematopoietic progenitors. Quantitative and semiquantitative WT1 reverse transcriptase polymerase chain reaction (RT-PCR) protocols have limitations in discriminating physiologic from pathologic overall WT1 expression levels in mononuclear cell preparations. Because of these limitations, reports conflict on the usefulness of long-term monitoring of WT1 expression in patients with acute leukemia. Real-time quantitative WT1 RT-PCR protocols, however, have been developed and tested in small series of patients with acute leukemia. Such protocols hold promise to enable evaluation of the individual treatment response (short-term monitoring) and early diagnosis of imminent relapse through the detection and long-term monitoring of minimal residual disease in patients with acute leukemia. These protocols also should facilitate the notoriously difficult distinction between eosinophilic leukemia and hypereosinophilic syndromes. Data on WT1 expression in leukemic blasts and their physiologic counterparts are discussed in light of clinical relevance.
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Wilms' Tumor Gene expression in human CD34+ hematopoietic progenitors during fetal development and early clonogenic growth.
Blood, 1997Co-Authors: Hans D. Menssen, Hans-j. Renkl, Michael Entezami, Eckhard ThielAbstract:To the Editor: The Wilms' Tumor Gene ( WT1 ) located on chromosome 11p131 encodes a transcription factor, which is involved in control of growth and differentiation of various cell types including hematopoietic cells.[2][1] It activates or suppresses the transcription of target Genes depending on
Yoshihiro Oka - One of the best experts on this subject based on the ideXlab platform.
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Induction of WT1 (Wilms' Tumor Gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression.
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Yoshihiro Oka, Taiichi Kyo, Hiroko Nakajima, Olga A Elisseeva, Manabu Kawakami, Yusuke Oji, Tetsuya Taguchi, Akihiro Tsuboi, Tadashi Osaki, Kazuhiro IkegameAbstract:The Wilms' Tumor Gene WT1 is overexpressed in leukemias and various types of solid Tumors, and the WT1 protein was demonstrated to be an attractive target antigen for immunotherapy against these malignancies. Here, we report the outcome of a phase I clinical study of WT1 peptide-based immunotherapy for patients with breast or lung cancer, myelodysplastic syndrome, or acute myeloid leukemia. Patients were intradermally injected with an HLA-A*2402-restricted, natural, or modified 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant at 0.3, 1.0, or 3.0 mg per body at 2-week intervals, with toxicity and clinical and immunological responses as the principal endpoints. Twenty-six patients received one or more WT1 vaccinations, and 18 of the 26 patients completed WT1 vaccination protocol with three or more injections of WT1 peptides. Toxicity consisted only of local erythema at the WT1 vaccine injection sites in patients with breast or lung cancer or acute myeloid leukemia with adequate normal hematopoiesis, whereas severe leukocytopenia occurred in patients with myelodysplastic syndrome with abnormal hematopoiesis derived from WT1-expressing, transformed hematopoietic stem cells. Twelve of the 20 patients for whom the efficacy of WT1 vaccination could be assessed showed clinical responses such as reduction in leukemic blast cells or Tumor sizes and/or Tumor markers. A clear correlation was observed between an increase in the frequencies of WT1-specific cytotoxic T lymphocytes after WT1 vaccination and clinical responses. It was therefore demonstrated that WT1 vaccination could induce WT1-specific cytotoxic T lymphocytes and result in cancer regression without damage to normal tissues.
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Cytotoxic T-Lymphocyte Responses Elicited to Wilms' Tumor Gene WT1 Product by DNA Vaccination
Journal of Clinical Immunology, 2000Co-Authors: Akihiro Tsuboi, Olga A Elisseeva, Yoshihiro Oka, Hiroyasu Ogawa, Katsuyuki Aozasa, Keiko Udaka, Tadamitsu Kishimoto, Hanfen Li, Kotomi Kawasaki, Haruo SugiyamaAbstract:We recently have reported that Wilms' Tumor Gene WT1 is highly expressed not only in leukemias but also in various types of solid Tumors and that WT1 protein is a novel Tumor antigen against which cytotoxic T lymphocytes (CTLs) can be elicited by immunization with 9-mer WT1 peptides capable of binding to major histocompatibility complex (MHC) class I molecules. In the present study, plasmid DNA encoding murine full-length WT1 protein was injected intramuscularly into C57BL/6 mice. The mice vaccinated with the WT1 plasmid DNA elicited CTLs against the WT1 protein, and the CTLs specifically killed WT1-expressing Tumor cells in a MHC class I-restricted manner. Furthermore, the vaccinated mice rejected the challenges of WT1-expressing Tumor cells and survived with no signs of autoimmunity caused by the CTLs. These results demonstrated that vaccination with the WT1 plasmid DNA can elicit CTL responses specific for the WT1 protein, resulting in the acquisition of rejection activity against challenges of WT1-expressing Tumor cells. This WT1 DNA vaccination may find clinical application for various types of solid Tumors as well as leukemias.
Olga A Elisseeva - One of the best experts on this subject based on the ideXlab platform.
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Induction of WT1 (Wilms' Tumor Gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression.
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Yoshihiro Oka, Taiichi Kyo, Hiroko Nakajima, Olga A Elisseeva, Manabu Kawakami, Yusuke Oji, Tetsuya Taguchi, Akihiro Tsuboi, Tadashi Osaki, Kazuhiro IkegameAbstract:The Wilms' Tumor Gene WT1 is overexpressed in leukemias and various types of solid Tumors, and the WT1 protein was demonstrated to be an attractive target antigen for immunotherapy against these malignancies. Here, we report the outcome of a phase I clinical study of WT1 peptide-based immunotherapy for patients with breast or lung cancer, myelodysplastic syndrome, or acute myeloid leukemia. Patients were intradermally injected with an HLA-A*2402-restricted, natural, or modified 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant at 0.3, 1.0, or 3.0 mg per body at 2-week intervals, with toxicity and clinical and immunological responses as the principal endpoints. Twenty-six patients received one or more WT1 vaccinations, and 18 of the 26 patients completed WT1 vaccination protocol with three or more injections of WT1 peptides. Toxicity consisted only of local erythema at the WT1 vaccine injection sites in patients with breast or lung cancer or acute myeloid leukemia with adequate normal hematopoiesis, whereas severe leukocytopenia occurred in patients with myelodysplastic syndrome with abnormal hematopoiesis derived from WT1-expressing, transformed hematopoietic stem cells. Twelve of the 20 patients for whom the efficacy of WT1 vaccination could be assessed showed clinical responses such as reduction in leukemic blast cells or Tumor sizes and/or Tumor markers. A clear correlation was observed between an increase in the frequencies of WT1-specific cytotoxic T lymphocytes after WT1 vaccination and clinical responses. It was therefore demonstrated that WT1 vaccination could induce WT1-specific cytotoxic T lymphocytes and result in cancer regression without damage to normal tissues.
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Cytotoxic T-Lymphocyte Responses Elicited to Wilms' Tumor Gene WT1 Product by DNA Vaccination
Journal of Clinical Immunology, 2000Co-Authors: Akihiro Tsuboi, Olga A Elisseeva, Yoshihiro Oka, Hiroyasu Ogawa, Katsuyuki Aozasa, Keiko Udaka, Tadamitsu Kishimoto, Hanfen Li, Kotomi Kawasaki, Haruo SugiyamaAbstract:We recently have reported that Wilms' Tumor Gene WT1 is highly expressed not only in leukemias but also in various types of solid Tumors and that WT1 protein is a novel Tumor antigen against which cytotoxic T lymphocytes (CTLs) can be elicited by immunization with 9-mer WT1 peptides capable of binding to major histocompatibility complex (MHC) class I molecules. In the present study, plasmid DNA encoding murine full-length WT1 protein was injected intramuscularly into C57BL/6 mice. The mice vaccinated with the WT1 plasmid DNA elicited CTLs against the WT1 protein, and the CTLs specifically killed WT1-expressing Tumor cells in a MHC class I-restricted manner. Furthermore, the vaccinated mice rejected the challenges of WT1-expressing Tumor cells and survived with no signs of autoimmunity caused by the CTLs. These results demonstrated that vaccination with the WT1 plasmid DNA can elicit CTL responses specific for the WT1 protein, resulting in the acquisition of rejection activity against challenges of WT1-expressing Tumor cells. This WT1 DNA vaccination may find clinical application for various types of solid Tumors as well as leukemias.
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Cancer Immunotherapy Targeting Wilms’ Tumor Gene WT1 Product
Journal of Immunology, 2000Co-Authors: Keiko Udaka, Olga A Elisseeva, Akihiro Tsuboi, Hiroyasu Ogawa, Katsuyuki Aozasa, Tadamitsu Kishimoto, Haruo SugiyamaAbstract: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.
