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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
#1
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...
October 19, 2017: 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
#2
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-analog-peptide-vaccine-after-multimodality-therapy-for-patients-with-malignant-pleural-mesothelioma
#3
Marjorie G Zauderer, Anne S Tsao, Tao Dao, Katherine S Panageas, W Victoria Lai, Andreas Rimner, Valerie W Rusch, Prasad S Adusumilli, Michelle S Ginsberg, Daniel R Gomez, David C Rice, Reza Mehran, David A Scheinberg, Lee M Krug
PURPOSE: Determine the 1-year progression-free survival (PFS) among patients with malignant pleural mesothelioma (MPM) receiving the WT1 peptide vaccine galinpepimut-S after multimodality therapy vs those receiving control adjuvants. PATIENTS AND METHODS: 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...
September 28, 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
#4
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
#5
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...
September 26, 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
#6
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
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 siRNAs for endogenous TCR genes...
August 31, 2017: Blood
https://www.readbyqxmd.com/read/28830889/dendritic-cell-vaccination-as-postremission-treatment-to-prevent-or-delay-relapse-in-acute-myeloid-leukemia
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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/27993090/wilms-tumor-1-wt1-targeted-cancer-vaccines-to-extend-survival-for-patients-with-pancreatic-cancer
#15
REVIEW
Shigeo Koido, Masato Okamoto, Shigetaka Shimodaira, Haruo Sugiyama
Despite novel chemotherapy treatments, pancreatic ductal adenocarcinoma (PDA) remains a lethal disease. New targeted cancer vaccines may represent a viable option for patients with PDA. The Wilms' tumor 1 (WT1) antigen is one of the most widely expressed tumor-associated antigens in various types of tumors, including PDA. Recent reports have indicated that WT1-targeted cancer vaccines for patients with PDA mediated a potent antitumor effect when combined with chemotherapy in preclinical and clinical studies...
November 2016: Immunotherapy
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
#16
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
#17
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/27659531/the-tumor-associated-antigen-rhamm-hmmr-cd168-is-expressed-by-monocyte-derived-dendritic-cells-and-presented-to-t-cells
#18
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/27634018/induction-of-immune-response-after-allogeneic-wilms-tumor-1-dendritic-cell-vaccination-and-donor-lymphocyte-infusion-in-patients-with-hematologic-malignancies-and-post-transplantation-relapse
#19
Nirali N Shah, David M Loeb, Hahn Khuu, David Stroncek, Tolu Ariyo, Mark Raffeld, Cindy Delbrook, Crystal L Mackall, Alan S Wayne, Terry J Fry
Relapse of hematologic malignancies is the primary cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HCT). Treatment for post-HCT relapse using donor lymphocyte infusion (DLI) has limited utility, particularly in the setting of acute leukemia, and can result in the development of graft-versus-host disease (GVHD). The Wilms' tumor 1 (WT1) gene product is a tumor-associated antigen that is expressed in acute leukemia and other hematologic malignancies, with limited expression in normal tissues...
September 12, 2016: Biology of Blood and Marrow Transplantation
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
#20
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
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