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https://www.readbyqxmd.com/read/29599343/feasibility-and-immune-response-of-wt1-peptide-vaccination-in-combination-with-ok-432-for-paediatric-solid-tumors
#1
Koichi Hirabayashi, Ryu Yanagisawa, Shoji Saito, Yumiko Higuchi, Terutsugu Koya, Kenji Sano, Shigeo Koido, Masato Okamoto, Haruo Sugiyama, Yozo Nakazawa, Shigetaka Shimodaira
BACKGROUND/AIM: Wilms' tumor 1 (WT1) peptide-based vaccination has been reported for its potential usefulness in targeting several cancers. The adjuvant drug OK-432 is known to have potent immunomodulation and therapeutic properties when applied in cancer treatment and may, thus, be important to trigger the appropriate immunological response in paediatric patients with a solid tumor that are vaccinated with a WT1 peptide. PATIENTS AND METHODS: Paediatric patients with a solid tumor were vaccinated with a WT1 peptide and OK-432 once every 2 weeks, for a total of seven times...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29599342/wt1-pulsed-dendritic-cell-vaccine-combined-with-chemotherapy-for-resected-pancreatic-cancer-in-a-phase-i-study
#2
Ryu Yanagisawa, Tomonobu Koizumi, Terutsugu Koya, Kenji Sano, Shigeo Koido, Kazuhiro Nagai, Masanori Kobayashi, Masato Okamoto, Haruo Sugiyama, Shigetaka Shimodaira
BACKGROUND/AIM: Wilms' tumor 1 (WT1) is a tumor-associated antigen highly expressed in cancer. We examined the safety of WT1-peptide pulsed dendritic cell (WT1-DC) vaccine in combination with chemotherapy in patients with surgically resected pancreatic cancer. PATIENTS AND METHODS: Eight patients with resectable pancreatic cancer undergoing surgery either combined with S-1 or S-1 plus gemcitabine therapy were enrolled. Immunohistochemical analysis of WT1 was performed in 34 cases of pancreatic cancer...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29386195/phase-2-trial-of-a-multivalent-wt1-peptide-vaccine-galinpepimut-s-in-acute-myeloid-leukemia
#3
Peter G Maslak, Tao Dao, Yvette Bernal, Suzanne M Chanel, Rong Zhang, Mark Frattini, Todd Rosenblat, Joseph G Jurcic, Renier J Brentjens, Maria E Arcila, Raajit Rampal, Jae H Park, Dan Douer, Laura Katz, Nicholas Sarlis, Martin S Tallman, David A Scheinberg
A National Cancer Institute consensus study on prioritization of cancer antigens ranked the Wilms tumor 1 (WT1) protein as the top immunotherapy target in cancer. We previously reported a pilot study of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia (AML) patients. We have now conducted a phase 2 study investigating this vaccine in adults with AML in first complete remission (CR1). Patients received 6 vaccinations administered over 10 weeks with the potential to receive 6 additional monthly doses if they remained in CR1...
February 13, 2018: Blood Advances
https://www.readbyqxmd.com/read/29358173/combination-gemcitabine-and-wt1-peptide-vaccination-improves-progression-free-survival-in-advanced-pancreatic-ductal-adenocarcinoma-a-phase-ii-randomized-study
#4
Sumiyuki Nishida, Takeshi Ishikawa, Shinichi Egawa, Shigeo Koido, Hiroaki Yanagimoto, Jun Ishii, Yoshihide Kanno, Satoshi Kokura, Hiroaki Yasuda, Mari Saito Oba, Maho Sato, Soyoko Morimoto, Fumihiro Fujiki, Hidetoshi Eguchi, Hiroaki Nagano, Atsushi Kumanogoh, Michiaki Unno, Masanori Kon, Hideaki Shimada, Kei Ito, Sadamu Homma, Yoshihiro Oka, Satoshi Morita, Haruo Sugiyama
We investigated the efficacy of a Wilms' tumor gene 1 (WT1) vaccine combined with gemcitabine (GEMWT1) and compared it with gemcitabine (GEM) monotherapy for advanced pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II study. We randomly assigned HLA-A*02:01- or HLA-A*24:02-positive patients with advanced PDAC to receive GEMWT1 or GEM. We assessed WT1-specific immune responses via delayed-type hypersensitivity (DTH) to the WT1 peptide and a tetramer assay to detect WT1-specific cytotoxic T lymphocytes (WT1-CTL)...
January 22, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29344432/wt1-peptide-vaccine-in-montanide-in-contrast-to-poly-iclc-is-able-to-induce-wt1-specific-immune-response-with-tcr-clonal-enrichment-in-myeloid-leukemia
#5
Hongtao Liu, Yuanyuan Zha, Noura Choudhury, Gregory Malnassy, Noreen Fulton, Margaret Green, Jae-Hyun Park, Yusuke Nakamura, Richard A Larson, Andres M Salazar, Olatoyosi Odenike, Thomas F Gajewski, Wendy Stock
Background: The optimal strategy for vaccination to induce CD8+ T cell responses against WT1 is not known. Methods: A pilot randomized study in HLA-A02+ patients to receive vaccination with WT1 in Montanide or in poly ICLC, a TLR3 agonist, to explore the novel immune adjuvant was conducted. Seven patients were randomized. Four patients received WT1 in Montanide, and three with WT1 in poly ICLC. Five patients were in morphologic remission and two had residual morphologic disease at the study entry...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29322496/wt1-peptide-based-immunotherapy-for-advanced-thymic-epithelial-malignancies
#6
Yusuke Oji, Masayoshi Inoue, Yoshito Takeda, Naoki Hosen, Yasushi Shintani, Manabu Kawakami, Takuya Harada, Yui Murakami, Miki Iwai, Mari Fukuda, Sumiyuki Nishida, Jun Nakata, Yoshiki Nakae, Satoshi Takashima, Toshiaki Shirakata, Hiroko Nakajima, Kana Hasegawa, Hiroshi Kida, Takashi Kijima, Soyoko Morimoto, Fumihiro Fujiki, Akihiro Tsuboi, Eiichi Morii, Satoshi Morita, Junichi Sakamoto, Atsushi Kumanogoh, Yoshihiro Oka, Meinoshin Okumura, Haruo Sugiyama
Thymic epithelial tumors are rare malignancies, and no optimal therapeutic regimen has been defined for patients with advanced disease. Patients with advanced thymic epithelial tumors, which were resistant or intolerable to prior therapies, were eligible for this study. Patients received 9 mer-WT1-derived peptide emulsified with Montanide ISA51 adjuvant via intradermal administration once a week as a monotherapy. After the 3-month-protocol treatment, the treatment was continued mostly at intervals of 2-4 weeks until disease progression or intolerable adverse events occurred...
June 1, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29048978/antitumor-effect-of-oral-cancer-vaccine-with-bifidobacterium-delivering-wt1-protein-to-gut-immune-system-is-superior-to-wt1-peptide-vaccine
#7
Toshiro Shirakawa, Koichi Kitagawa
Despite the revolutionary progress of immune checkpoint inhibitors (CPIs) for cancer immunotherapy, CPIs are effective only in a subset of patients. Combining CPIs and cancer vaccines to achieve better clinical outcomes is a reasonable approach since CPI enhances cancer vaccine-induced tumor-associated antigen (TAA) specific CTL. Among the various TAAs so far identified, WT1 protein is one of the most promising TAAs as a cancer vaccine target. Until now clinical trials of WT1 vaccine have demonstrated only modest clinical efficacy...
January 2, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29041012/wilms-tumor-gene-1-wt1-peptide-vaccine-therapy-for-hematological-malignancies-from-ctl-epitope-identification-to-recent-progress-in-clinical-studies-including-a-cure-oriented-strategy
#8
Yoshihiro Oka, Akihiro Tsuboi, Jun Nakata, Sumiyuki Nishida, Naoki Hosen, Atsushi Kumanogoh, Yusuke Oji, Haruo Sugiyama
The identification of human Wilms' tumor gene 1 (WT1) protein-derived cytotoxic T lymphocyte (CTL) epitopes and the in vivo efficacy of WT1 peptide-based immunotherapy in a mouse model were reported in 2000. This successful basic research led to clinical studies of a WT1 peptide vaccine, and a positive impact on clinical response was first demonstrated in 2003 in the form of a reduction in blast cells of vaccine-treated patients with myelodysplastic syndromes (MDS). Since then, data on WT1 peptide vaccine-treated patients with immunological and/or clinical response have been accumulated...
2017: Oncology Research and Treatment
https://www.readbyqxmd.com/read/28972039/a-randomized-phase-ii-trial-of-adjuvant-galinpepimut-s-wt-1-analogue-peptide-vaccine-after-multimodality-therapy-for-patients-with-malignant-pleural-mesothelioma
#9
Marjorie G Zauderer, Anne S Tsao, Tao Dao, Katherine Panageas, W Victoria Lai, Andreas Rimner, Valerie W Rusch, Prasad S Adusumilli, Michelle S Ginsberg, Daniel Gomez, David Rice, Reza Mehran, David A Scheinberg, Lee M Krug
Purpose: Determine the 1-year progression-free survival (PFS) rate among patients with malignant pleural mesothelioma (MPM) receiving the WT1 peptide vaccine galinpepimut-S after multimodality therapy versus those receiving control adjuvants. Experimental Design: This double-blind, controlled, two center phase II trial randomized MPM patients after surgery and another treatment modality to galinpepimut-S with GM-CSF and Montanide or GM-CSF and Montanide alone. An improvement in 1-year PFS from 50% to 70% was the predefined efficacy threshold, and 78 patients total were planned...
December 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28950074/significance-of-wilms-tumor-1-antigen-as-a-cancer-vaccine-for-pancreatic-cancer
#10
Shigeo Koido, Masato Okamoto, Masanori Kobayashi, Shigetaka Shimodaira, Haruo Sugiyama
Pancreatic ductal adenocarcinoma (PDA) is characterized by a very poor prognosis, despite novel chemotherapeutic treatments. Moreover, the majority of PDA patients with complete surgical resection show recurrence within 5 years of resection. Therefore, new targeted cancer vaccines are urgently needed to extend PDA patient survival. The Wilms' tumor 1 (WT1) antigen was identified as an excellent antigen in a list of 75 tumor-associated antigens by a National Cancer Institute prioritization project based on several factors, such as therapeutic function...
August 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28949050/phase-1-2-study-of-the-wt1-peptide-cancer-vaccine-wt4869-in-patients-with-myelodysplastic-syndrome
#11
MULTICENTER STUDY
Yasunori Ueda, Michinori Ogura, Shigesaburo Miyakoshi, Takahiro Suzuki, Yuji Heike, Shuzo Tagashira, Satoru Tsuchiya, Kazuma Ohyashiki, Yasushi Miyazaki
WT4869 is a synthetic peptide vaccine derived from the Wilms' tumor gene 1 (WT1) protein. This phase 1/2 open-label study evaluated the safety and efficacy of WT4869, and biomarkers for response, in patients with myelodysplastic syndrome. WT4869 (5-1200 μg/dose) was administered intradermally every 2 weeks, according to a 3 + 3 dose-escalation method in higher-risk (International Prognostic Scoring System score ≥1.5) or lower-risk (score <1.5) red blood cell transfusion-dependent patients with myelodysplastic syndrome...
December 2017: Cancer Science
https://www.readbyqxmd.com/read/28860210/safety-and-persistence-of-wt1-specific-t-cell-receptor-gene-transduced-lymphocytes-in-patients-with-aml-and-mds
#12
Isao Tawara, Shinichi Kageyama, Yoshihiro Miyahara, Hiroshi Fujiwara, Tetsuya Nishida, Yoshiki Akatsuka, Hiroaki Ikeda, Kazushi Tanimoto, Seitaro Terakura, Makoto Murata, Yoko Inaguma, Masahiro Masuya, Naoki Inoue, Tomohide Kidokoro, Sachiko Okamoto, Daisuke Tomura, Hideto Chono, Ikuei Nukaya, Junichi Mineno, Tomoki Naoe, Nobuhiko Emi, Masaki Yasukawa, Naoyuki Katayama, Hiroshi Shiku
Wilms' tumor 1 (WT1) is constantly expressed in leukemic cells of acute leukemia and myelodysplastic syndrome (MDS). A T-cell receptor (TCR) that specifically reacts with WT1 peptide in the context of HLA-A*24:02 has been identified. We conducted a first-in-human trial of TCR-gene transduced T-cell (TCR-T-cell) transfer in patients with refractory acute myeloblastic leukemia (AML) and high-risk MDS to investigate the safety and cell kinetics of the T cells. The WT1-specific TCR-gene was transduced to T cells using a retroviral vector encoding small interfering RNAs for endogenous TCR genes...
November 2, 2017: Blood
https://www.readbyqxmd.com/read/28830889/dendritic-cell-vaccination-as-postremission-treatment-to-prevent-or-delay-relapse-in-acute-myeloid-leukemia
#13
Sébastien Anguille, Ann L Van de Velde, Evelien L Smits, Viggo F Van Tendeloo, Gunnar Juliusson, Nathalie Cools, Griet Nijs, Barbara Stein, Eva Lion, Ann Van Driessche, Irma Vandenbosch, Anke Verlinden, Alain P Gadisseur, Wilfried A Schroyens, Ludo Muylle, Katrien Vermeulen, Marie-Berthe Maes, Kathleen Deiteren, Ronald Malfait, Emma Gostick, Martin Lammens, Marie M Couttenye, Philippe Jorens, Herman Goossens, David A Price, Kristin Ladell, Yoshihiro Oka, Fumihiro Fujiki, Yusuke Oji, Haruo Sugiyama, Zwi N Berneman
Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms' tumor 1 ( WT1 ) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109...
October 12, 2017: Blood
https://www.readbyqxmd.com/read/28435676/understanding-cd8-t-cell-responses-toward-the-native-and-alternate-hla-a-02-01-restricted-wt1-epitope
#14
Thi Ho Nguyen, Amabel Cl Tan, Sue D Xiang, Anne Goubier, Kim L Harland, E Bridie Clemens, Magdalena Plebanski, Katherine Kedzierska
The Wilms' tumor 1 (WT1) antigen is expressed in solid and hematological malignancies, but not healthy tissues, making it a promising target for cancer immunotherapies. Immunodominant WT1 epitopes, the native HLA-A2/WT1126-134 (RMFPNAPYL) (HLA-A2/RMFPNAPYL epitope (WT1A)) and its modified variant YMFPNAPYL (HLA-A2/YMFPNAPYL epitope (WT1B)), can induce WT1-specific CD8(+) T cells, although WT1B is more stably bound to HLA-A*02:01. Here, to further determine the benefits of those two targets, we assessed the naive precursor frequencies; immunogenicity and cross-reactivity of CD8(+) T cells directed toward these two WT1 epitopes...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28321480/a-new-peptide-vaccine-ocv-501-in-vitro-pharmacology-and-phase-1-study-in-patients-with-acute-myeloid-leukemia
#15
MULTICENTER STUDY
Yukio Kobayashi, Toru Sakura, Shuichi Miyawaki, Kazuyuki Toga, Shinji Sogo, Yuji Heike
Wilms' tumor 1 (WT1) is a promising target of new immunotherapies for acute myeloid leukemia (AML) as well as for other cancers. OCV-501 is a helper peptide derived from the WT1 protein. OCV-501 induced OCV-501-specific Type 1 T-helper (Th1) responses dose-dependently and stimulated helper activity of the specific Th1 cells in peripheral blood mononuclear cells from healthy donors. OCV-501 also enhanced the increase in WT1-killer peptide-specific cytotoxic T lymphocytes. OCV-501 stimulated the OCV-501-specific Th1 clones in an HLA class-II restricted manner and formed a complex with HLA class-II protein...
July 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28299466/development-of-oral-cancer-vaccine-using-recombinant-bifidobacterium-displaying-wilms-tumor-1-protein
#16
Koichi Kitagawa, Tsugumi Oda, Hiroki Saito, Ayame Araki, Reina Gonoi, Katsumi Shigemura, Yoshiko Hashii, Takane Katayama, Masato Fujisawa, Toshiro Shirakawa
Several types of vaccine-delivering tumor-associated antigens (TAAs) have been developed in basic and clinical research. Wilms' tumor 1 (WT1), identified as a gene responsible for pediatric renal neoplasm, is one of the most promising TAA for cancer immunotherapy. Peptide and dendritic cell-based WT1 cancer vaccines showed some therapeutic efficacy in clinical and pre-clinical studies but as yet no oral WT1 vaccine can be administrated in a simple and easy way. In the present study, we constructed a novel oral cancer vaccine using a recombinant Bifidobacterium longum displaying WT1 protein...
June 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28263240/peptide-pulsed-dendritic-cell-vaccine-in-combination-with-carboplatin-and-paclitaxel-chemotherapy-for-stage-iv-melanoma
#17
Keitaro Fukuda, Takeru Funakoshi, Toshiharu Sakurai, Yoshio Nakamura, Mariko Mori, Keiji Tanese, Akiko Tanikawa, Junichi Taguchi, Tomonobu Fujita, Masato Okamoto, Masayuki Amagai, Yutaka Kawakami
In this study, we aimed to evaluate the feasibility and efficacy of peptide-pulsed dendritic cell (DC) vaccine in combination with carboplatin and paclitaxel chemotherapy (DCCP) for patients with stage IV melanoma previously treated with dacarbazine-containing regimen. Six HLA-A24 and 3 HLA-A02 patients were treated with carboplatin (area under the curve 5) and paclitaxel (175 mg/m) on day 1 and DCs (2×10 cells) pulsed with Wilms tumor gene 1 (WT1), gp100, tyrosinase, and either MAGE-A3 (for HLA-A24) or MAGE-A2 (for HLA-A02) peptides on days 8 and 22 in 28-day cycle for up to three cycles...
August 2017: Melanoma Research
https://www.readbyqxmd.com/read/28237837/a-novel-dna-vaccine-platform-enhances-neo-antigen-like-t-cell-responses-against-wt1-to-break-tolerance-and-induce-anti-tumor-immunity
#18
Jewell N Walters, Bernadette Ferraro, Elizabeth K Duperret, Kimberly A Kraynyak, Jaemi Chu, Ashley Saint-Fleur, Jian Yan, Hy Levitsky, Amir S Khan, Niranjan Y Sardesai, David B Weiner
Tumor-associated antigens have emerged as important immunotherapeutic targets in the fight against cancer. Germline tumor antigens, such as WT1, Wilms' tumor gene 1, are overexpressed in many human malignancies but have low expression in somatic tissues. Recent vaccination approaches to target WT1 have been hampered by poor in vivo immune potency, likely due to the conserved self-antigen nature of WT1. In this study, we use a novel synthetic micro-consensus SynCon DNA vaccine approach with the goal of breaking tolerance and increasing vaccine immune potency...
April 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28176175/safety-and-immunogenicity-of-neoadjuvant-treatment-using-wt1-immunotherapeutic-in-combination-with-standard-therapy-in-patients-with-wt1-positive-stage-ii-iii-breast-cancer-a-randomized-phase-i-study
#19
RANDOMIZED CONTROLLED TRIAL
M Higgins, G Curigliano, V Dieras, S Kuemmel, G Kunz, P A Fasching, M Campone, T Bachelot, P Krivorotko, S Chan, A Ferro, L Schwartzberg, M Gillet, P M De Sousa Alves, V Wascotte, F F Lehmann, P Goss
PURPOSE: This Phase I, multicenter, randomized study (ClinicalTrials.gov NCT01220128) evaluated the safety and immunogenicity of recombinant Wilms' tumor 1 (WT1) protein combined with the immunostimulant AS15 (WT1-immunotherapeutic) as neoadjuvant therapy administered concurrently with standard treatments in WT1-positive breast cancer patients. METHODS: Patients were treated in 4 cohorts according to neoadjuvant treatment (A: post-menopausal, hormone receptor [HR]-positive patients receiving aromatase inhibitors; B: patients receiving chemotherapy; C: HER2-overexpressing patients on trastuzumab-chemotherapy combination; D: HR-positive/HER2-negative patients on chemotherapy)...
April 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28116121/syndecan-4-as-a-biomarker-to-predict-clinical-outcome-for-glioblastoma-multiforme-treated-with-wt1-peptide-vaccine
#20
Satoshi Takashima, Yoshihiro Oka, Fumihiro Fujiki, Soyoko Morimoto, Hiroko Nakajima, Yoshiki Nakae, Jun Nakata, Sumiyuki Nishida, Naoki Hosen, Naoya Tatsumi, Kenji Mizuguchi, Naoya Hashimoto, Yusuke Oji, Akihiro Tsuboi, Atsushi Kumanogoh, Haruo Sugiyama
AIM: In cancer immunotherapy, biomarkers are important for identification of responsive patients. This study was aimed to find biomarkers that predict clinical outcome of WT1 peptide vaccination. MATERIALS & METHODS: Candidate genes that were expressed differentially between long- and short-term survivors were identified by cDNA microarray analysis of peripheral blood mononuclear cells that were extracted from 30 glioblastoma patients (discovery set) prior to vaccination and validated by quantitative RT-PCR using discovery set and different 23 patients (validation set)...
December 2016: Future Science OA
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