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WT1 and immunotherapy

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https://www.readbyqxmd.com/read/28544366/enumeration-of-wt1-specific-cd8-t-cells-for-clinical-application-using-an-mhc-streptamer-based-no-wash-single-platform-flow-cytometric-assay
#1
Sarah Matko, Madeleine Teichert, Antje Tunger, Marc Schmitz, Martin Bornhauser, Torsten Tonn, Marcus Odendahl
The advent of novel strategies to generate leukemia-associated-antigen (LAA)-specific T cells for adoptive immunotherapies creates a demand for standardized good laboratory practice (GLP)-compliant enumeration assays to provide a secure clinical environment-whether it is to identify potential donors, define therapeutic doses for transplantation, or monitor clinical success. Here, we introduce a no-wash assay based on single-platform cell enumeration and Streptamer staining to determine the Wilms' tumor antigen 1 (WT1)-specific T cell immunity in clinical samples...
May 25, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28435676/understanding-cd8-t-cell-responses-toward-the-native-and-alternate-hla-a-02-01-restricted-wt1-epitope
#2
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/28344864/an-immunogenic-wt1-derived-peptide-that-induces-t-cell-response-in-the-context-of-hla-a-02-01-and-hla-a-24-02-molecules
#3
Tao Dao, Tatyana Korontsvit, Victoria Zakhaleva, Casey Jarvis, Patrizia Mondello, Claire Oh, David A Scheinberg
The Wilms' tumor oncogene protein (WT1) is a highly validated tumor antigen for immunotherapy. WT1-targeted immunotherapy has been extensively explored in multiple human trials in various cancers. However, clinical investigations using WT1 epitopes have generally focused on two peptides, HLA-restricted to HLA-A*02:01 or HLA-A*24:02. The goal of this study was to identify new epitopes derived from WT1, to expand the potential use of WT1 as a target of immunotherapy. Using computer-based MHC-binding algorithms and in vitro validation of the T cell responses specific for the identified peptides, we found that a recently identified HLA-A*24:02-binding epitope (239-247), NQMNLGATL (NQM), was also a strong CD8(+) T cell epitope for HLA-A*02:01 molecule...
2017: Oncoimmunology
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
#4
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...
March 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28299466/development-of-oral-cancer-vaccine-using-recombinant-bifidobacterium-displaying-wilms-tumor-1-protein
#5
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...
March 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28116121/syndecan-4-as-a-biomarker-to-predict-clinical-outcome-for-glioblastoma-multiforme-treated-with-wt1-peptide-vaccine
#6
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
https://www.readbyqxmd.com/read/27941286/adoptive-immunotherapy-utilizing-cancer-antigen-specific-t-cell-receptors
#7
Kazushi Tanimoto, Hiroshi Fujiwara
Synthetic immunology based on rapidly-advancing gene-engineering and immunobiology has made novel anticancer adoptive immunotherapies, using gene-modified T lymphocytes to express cancer antigen-specific receptors, a reality. Various technological innovations have overcome recent difficulties and achieved clear and long-lasting clinical efficacy against tumors, while seeking more powerful effector gene-modified T cells has yielded serious treatment-related adverse events. In this article, along with introducing our clinical trial for a novel anti-leukemia adoptive immunotherapy regimen using gene-modified autologous lymphocytes to express leukemia antigen Wilms Tumor 1(WT1)-specific T cell receptor (TCR) against refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we provide an overview of the current status of this emerging treatment option and discuss its future form in the context of neoantigens encoded by mutated genes in cancer cells and immune checkpoint inhibitors...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27924074/optimized-t-cell-receptor-mimic-chimeric-antigen-receptor-t-cells-directed-toward-the-intracellular-wilms-tumor-1-antigen
#8
S Rafiq, T J Purdon, A F Daniyan, M Koneru, T Dao, C Liu, D A Scheinberg, R J Brentjens
CD19-directed chimeric antigen receptor (CAR) T cells are clinically effective in a limited set of leukemia patients. However, CAR T-cell therapy thus far has been largely restricted to targeting extracellular tumor-associated antigens (TAA). Herein, we report a T-cell receptor-mimic (TCRm) CAR, termed WT1-28z, that is reactive to a peptide portion of the intracellular onco-protein Wilms Tumor 1(WT1), as it is expressed on the surface of the tumor cell in the context of HLA-A*02:01. T cells modified to express WT1-28z specifically targeted and lysed HLA-A*02:01+ WT1+ tumors and enhanced survival of mice engrafted with HLA-A*02:01+, WT1+ leukemia or ovarian tumors...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27896368/targeting-of-the-wt191-138-fragment-to-human-dendritic-cells-improves-leukemia-specific-t-cell-responses-providing-an-alternative-approach-to-wt1-based-vaccination
#9
Nergui Dagvadorj, Anne Deuretzbacher, Daniela Weisenberger, Elke Baumeister, Johannes Trebing, Isabell Lang, Carolin Köchel, Markus Kapp, Kerstin Kapp, Andreas Beilhack, Thomas Hünig, Hermann Einsele, Harald Wajant, Götz Ulrich Grigoleit
Due to its immunogenicity and overexpression concomitant with leukemia progression, Wilms tumor protein 1 (WT1) is of particular interest for immunotherapy of AML relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, WT1-specific T-cell responses have mainly been induced by vaccination with peptides presented by certain HLA alleles. However, this approach is still not widely applicable in clinical practice due to common limitations of HLA restriction. Dendritic cell (DC) vaccines electroporated with mRNA encoding full-length protein have also been tested for generating WT1-derived peptides for presentation to T-cells...
March 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27760951/-wt1-class-i-peptide-wt1-class-ii-peptide-pulsed-dendritic-cell-therapy-efficacy-in-60-patients-with-a-wide-range-of-advanced-cancers
#10
Yoichi Kato
We assessed the efficacy of WT1 class I peptide and WT1 class II peptide pulsed dendritic cell(DC)therapy for a wide range of advanced cancers. This retrospective study included 60 advanced cancer patients who were vaccinated 5times or more in this clinic between September 2013 and December 2015. The clinical response was examined. This treatment was approved by the ethics panel at this institution. Sixty patients were injected an average of 6.15times with dendritic cells(DCs) (2.6×10 / 7 cells/injection)...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27757306/mechanisms-of-leukemia-resistance-to-antibody-dependent-cellular-cytotoxicity
#11
Leonid Dubrovsky, Elliott Joseph Brea, Dmitry Pankov, Emily Casey, Tao Dao, Cheng Liu, David A Scheinberg
Specific immunotherapy for acute leukemia remains a great unmet need. Native unmodified monoclonal antibody therapies, while promising, are inadequately effective for these malignancies, and multiple mechanisms for failure have been described. Antibody-dependent cellular cytotoxicity or phagocytosis is the primary modality of mAb-mediated cell killing in vivo, but ultimately leads to relapse of the leukemias, in model systems and in humans. By use of a T-cell receptor mimic mAb ESKM, derived against a WT1 peptide expressed in complex with HLA-A*02:01, whose only mechanism of therapeutic action is ADCC, we evaluated the mechanisms of leukemic relapse from its potent therapeutic action in mouse xenograft models of human leukemia...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27659531/the-tumor-associated-antigen-rhamm-hmmr-cd168-is-expressed-by-monocyte-derived-dendritic-cells-and-presented-to-t-cells
#12
Yannick Willemen, Johan M J Van den Bergh, Sarah M Bonte, Sébastien Anguille, Carlo Heirman, Barbara M H Stein, Herman Goossens, Tessa Kerre, Kris Thielemans, Marc Peeters, Viggo F I Van Tendeloo, Evelien L J Smits, Zwi N Berneman
We formerly demonstrated that vaccination with Wilms' tumor 1 (WT1)-loaded autologous monocyte-derived dendritic cells (mo-DCs) can be a well-tolerated effective treatment in acute myeloid leukemia (AML) patients. Here, we investigated whether we could introduce the receptor for hyaluronic acid-mediated motility (RHAMM/HMMR/CD168), another clinically relevant tumor-associated antigen, into these mo-DCs through mRNA electroporation and elicit RHAMM-specific immune responses. While RHAMM mRNA electroporation significantly increased RHAMM protein expression by mo-DCs, our data indicate that classical mo-DCs already express and present RHAMM at sufficient levels to activate RHAMM-specific T cells, regardless of electroporation...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27622060/biphasic-function-of-tlr3-adjuvant-on-tumor-and-spleen-dendritic-cells-promotes-tumor-t-cell-infiltration-and-regression-in-a-vaccine-therapy
#13
Masahiro Azuma, Yohei Takeda, Hiroko Nakajima, Haruo Sugiyama, Takashi Ebihara, Hiroyuki Oshiumi, Misako Matsumoto, Tsukasa Seya
Successful cancer immunotherapy necessitates T cell proliferation and infiltration into tumor without exhaustion, a process closely links optimal maturation of dendritic cells (DC), and adjuvant promotes this process as an essential prerequisite. Poly(I:C) has contributed to adjuvant immunotherapy that evokes an antitumor response through the Toll-loke receptor 3 (TLR3)/TICAM-1 pathway in DC. However, the mechanism whereby Poly(I:C) acts on DC for T cell proliferation and migration remains undetermined. Subcutaneous injection of Poly(I:C) regressed implant tumors (WT1-C1498 or OVA-EG7) in C57BL/6 mice, which coincided with tumor-infiltration of CD8(+) T cells...
August 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27466479/immunotherapy-in-acute-leukemias-implications-and-perspectives-using-wt1-antigen
#14
REVIEW
Guilherme Cesar Martelossi Cebinelli, Nathália DE Sousa Pereira, Michelle Mota Sena, Carlos Eduardo Coral DE Oliveira, Thiago Cezar Fujita, Sérgio Paulo Dejato DA Rocha, Francisco José DE Abreu Oliveira, Poliana Camila Marinello, Maria Angelica Ehara Watanabe
The WT1 gene encodes a transcription factor involved in regulation of many cellular processes, including proliferation, differentiation, mRNA processing and apoptosis, besides acting as a transcription repressor of growth factors and their receptors' genes. This gene is expressed at high levels in several types of cancers, including acute leukemias. In this regard, many studies have identified WT1 protein as a tumor antigen, considered a target molecule for clinical application in human acute leukemias. Immunotherapy using WT1 antigen has been effective in stimulating immune responses against leukemic cells...
August 2016: Anticancer Research
https://www.readbyqxmd.com/read/27417973/immunotherapy-targeting-wt1-designing-a-protocol-for-wt1-peptide-based-cancer-vaccine
#15
Sumiyuki Nishida, Haruo Sugiyama
There is much current excitement about the potential of cancer immunotherapy. WT1 is high on the National Cancer Institute's list of priority antigens for immune therapy. In this chapter we describe a protocol for a clinical trial using a WT1 peptide-based cancer vaccine.
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27354645/immunohistochemical-analysis-of-wt1-antigen-expression-in-various-solid-cancer-cells
#16
Keiko Naitoh, Takashi Kamigaki, Eriko Matsuda, Hiroshi Ibe, Sachiko Okada, Eri Oguma, Yoshihiro Kinoshita, Rishu Takimoto, Kaori Makita, Shun Ogasawara, Shigenori Goto
For a peptide-pulsed dendritic cell (DC) vaccine to work effectively in cancer treatment, it is significant that the target protein is expressed in cancer cells. Wilms' tumor 1 (WT1) has been identified as a molecular target for immune cell therapy of cancer. We evaluated the protein expression levels of WT1 in various solid tumors, as well as mucin 1 (MUC1) or major histocompatibility complex (MHC) class l molecules. Seven hundred and thirty-eight patients whose tissue samples were examined by immunohistochemical analysis agreed to undergo DC vaccine therapy...
July 2016: Anticancer Research
https://www.readbyqxmd.com/read/27323861/expression-of-tumor-antigens-on-primary-ovarian-cancer-cells-compared-to-established-ovarian-cancer-cell-lines
#17
Kamila Kloudová, Hana Hromádková, Simona Partlová, Tomáš Brtnický, Lukáš Rob, Jiřina Bartůňková, Michal Hensler, Michael J Halaška, Radek Špíšek, Anna Fialová
In order to select a suitable combination of cancer cell lines as an appropriate source of antigens for dendritic cell-based immunotherapy of ovarian cancer, we analyzed the expression level of 21 tumor associated antigens (BIRC5, CA125, CEA, DDX43, EPCAM, FOLR1, Her-2/neu, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MUC-1, NY-ESO-1, PRAME, p53, TPBG, TRT, WT1) in 4 established ovarian cancer cell lines and in primary tumor cells isolated from the high-grade serous epithelial ovarian cancer tissue...
July 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27302479/minimal-residual-disease-monitoring-and-preemptive-immunotherapy-in-myelodysplastic-syndrome-after-allogeneic-hematopoietic-stem-cell-transplantation
#18
Xiao-Dong Mo, Ya-Zhen Qin, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Kai-Yan Liu, Xiao-Jun Huang
This study investigated the efficacy of minimal residual disease (MRD) monitoring and MRD-directed preemptive immunotherapy in high-risk myelodysplastic syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (HSCT). MRD assessment consisted of Wilms' tumor gene 1 (WT1) detection with PCR and leukemia-associated immunophenotypic pattern examination with multiparameter flow cytometry (FCM). Post-HSCT, 31 patients were positive for WT1, and 8, for FCM; positivity for WT1 (18.6 vs...
August 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27236806/mrna-electroporation-of-dendritic-cells-with-wt1-survivin-and-trimix-a-mixture-of-catlr4-cd40l-and-cd70
#19
An Coosemans, Sandra Tuyaerts, Kim Morias, Jurgen Corthals, Carlo Heirman, Kris Thielemans, Stefaan W Van Gool, Ignace Vergote, Frédéric Amant
The immune system is a crucial player in the development of cancer. Once it is in imbalance and immunosuppressive mechanisms supporting tumor growth take over control, dendritic cell immunotherapy might offer a solution to restore the balance. There are several methods to manufacture dendritic cells but none of them has yet proven to be superior to others. In this chapter, we discuss the methodology using electroporation of mRNA encoding Wilms' tumor gene 1, survivin, and TriMix (mixture of caTLR4, CD40L, and CD70) to simultaneously load and mature dendritic cells...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27181332/bcr-abl-specific-cd4-t-helper-cells-promote-the-priming-of-antigen-specific-cytotoxic-t-cells-via-dendritic-cells
#20
Norihiro Ueda, Rong Zhang, Minako Tatsumi, Tian-Yi Liu, Shuichi Kitayama, Yutaka Yasui, Shiori Sugai, Tatsuaki Iwama, Satoru Senju, Seiji Okada, Tetsuya Nakatsura, Kiyotaka Kuzushima, Hitoshi Kiyoi, Tomoki Naoe, Shin Kaneko, Yasushi Uemura
The advent of tyrosine kinase inhibitor (TKI) therapy markedly improved the outcome of patients with chronic-phase chronic myeloid leukemia (CML). However, the poor prognosis of patients with advanced-phase CML and the lifelong dependency on TKIs are remaining challenges; therefore, an effective therapeutic has been sought. The BCR-ABL p210 fusion protein's junction region represents a leukemia-specific neoantigen and is thus an attractive target for antigen-specific T-cell immunotherapy. BCR-ABL p210 fusion-region-specific CD4(+) T-helper (Th) cells possess antileukemic potential, but their function remains unclear...
May 16, 2016: Cellular & Molecular Immunology
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