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WT1 vaccine

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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
#1
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...
November 28, 2016: 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
#2
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
#3
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...
September 21, 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
#4
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
#5
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/27417973/immunotherapy-targeting-wt1-designing-a-protocol-for-wt1-peptide-based-cancer-vaccine
#6
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
#7
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/27170523/association-of-wt1-igg-antibody-against-wt1-peptide-with-prolonged-survival-in-glioblastoma-multiforme-patients-vaccinated-with-wt1-peptide
#8
Yusuke Oji, Naoya Hashimoto, Akihiro Tsuboi, Yui Murakami, Miki Iwai, Naoki Kagawa, Yasuyoshi Chiba, Shuichi Izumoto, Olga Elisseeva, Ryo Ichinohasama, Junichi Sakamoto, Satoshi Morita, Hiroko Nakajima, Satoshi Takashima, Yoshiki Nakae, Jun Nakata, Manabu Kawakami, Sumiyuki Nishida, Naoki Hosen, Fumihiro Fujiki, Soyoko Morimoto, Mayuko Adachi, Masahiro Iwamoto, Yoshihiro Oka, Toshiki Yoshimine, Haruo Sugiyama
We previously evaluated Wilms' tumor gene 1 (WT1) peptide vaccination in a large number of patients with leukemia or solid tumors and have reported that HLA-A*24:02 restricted, 9-mer WT1-235 peptide (CYTWNQMNL) vaccine induces cellular immune responses and elicits WT1-235-specific cytotoxic T lymphocytes (CTLs). However, whether this vaccine induces humoral immune responses to produce WT1 antibody remains unknown. Thus, we measured IgG antibody levels against the WT1-235 peptide (WT1-235 IgG antibody) in patients with glioblastoma multiforme (GBM) receiving the WT1 peptide vaccine...
September 15, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27033213/generation-and-cryopreservation-of-clinical-grade-wilms-tumor-1-mrna-loaded-dendritic-cell-vaccines-for-cancer-immunotherapy
#9
Evelien L J M Smits, Barbara Stein, Griet Nijs, Eva Lion, Viggo F Van Tendeloo, Yannick Willemen, Sébastien Anguille, Zwi N Berneman
First described in the 1970s, dendritic cells (DC) are currently subjects of intense investigation to exploit their unique antigen-presenting and immunoregulatory capacities. In cancer, DC show promise to elicit or amplify immune responses directed against cancer cells by activating natural killer (NK) cells and tumor antigen-specific T cells. Wilms' tumor 1 (WT1) protein is a tumor-associated antigen that is expressed in a majority of cancer types and has been designated as an antigen of major interest to be targeted in clinical cancer immunotherapy trials...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/26938944/a-high-avidity-wt1-reactive-t-cell-receptor-mediates-recognition-of-peptide-and-processed-antigen-but-not-naturally-occurring-wt1-positive-tumor-cells
#10
Adnan Jaigirdar, Steven A Rosenberg, Maria Parkhurst
Wilms tumor gene 1 (WT1) is an attractive target antigen for cancer immunotherapy because it is overexpressed in many hematologic malignancies and solid tumors but has limited, low-level expression in normal adult tissues. Multiple HLA class I and class II restricted epitopes have been identified in WT1, and multiple investigators are pursuing the treatment of cancer patients with WT1-based vaccines and adoptively transferred WT1-reactive T cells. Here we isolated an HLA-A*0201-restricted WT1-reactive T-cell receptor (TCR) by stimulating peripheral blood lymphocytes of healthy donors with the peptide WT1:126-134 in vitro...
April 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/26855819/dendritic-cell-based-vaccine-for-pancreatic-cancer-in-japan
#11
REVIEW
Masato Okamoto, Masanori Kobayashi, Yoshikazu Yonemitsu, Shigeo Koido, Sadamu Homma
"Vaccell" is a dendritic cell (DC)-based cancer vaccine which has been established in Japan. The DCs play central roles in deciding the direction of host immune reactions as well as antigen presentation. We have demonstrated that DCs treated with a streptococcal immune adjuvant OK-432, produce interleukin-12, induce Th1-dominant state, and elicit anti-tumor effects, more powerful than those treated with the known DC-maturating factors. We therefore decided to mature DCs by the OK-432 for making an effective DC vaccine, Vaccell...
February 6, 2016: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/26824052/electroporated-antigen-encoding-mrna-is-not-a-danger-signal-to-human-mature-monocyte-derived-dendritic-cells
#12
Stefanie Hoyer, Kerstin F Gerer, Isabell A Pfeiffer, Sabrina Prommersberger, Sandra Höfflin, Tanushree Jaitly, Luca Beltrame, Duccio Cavalieri, Gerold Schuler, Julio Vera, Niels Schaft, Jan Dörrie
For therapeutic cancer vaccination, the adoptive transfer of mRNA-electroporated dendritic cells (DCs) is frequently performed, usually with monocyte-derived, cytokine-matured DCs (moDCs). However, DCs are rich in danger-sensing receptors which could recognize the exogenously delivered mRNA and induce DC activation, hence influencing the DCs' immunogenicity. Therefore, we examined whether electroporation of mRNA with a proper cap and a poly-A tail of at least 64 adenosines had any influence on cocktail-matured moDCs...
2015: Journal of Immunology Research
https://www.readbyqxmd.com/read/26721227/wilms-tumor-protein-1-wt1-not-only-a-diagnostic-but-also-a-prognostic-marker-in-high-grade-serous-ovarian-carcinoma
#13
Eliane Tabea Taube, Carsten Denkert, Jalid Sehouli, Catarina Alisa Kunze, Manfred Dietel, Ioana Braicu, Anne Letsch, Silvia Darb-Esfahani
AIMS: Wilms tumor protein 1 (WT1) expression is used in gynecological pathology as a diagnostic marker of serous differentiation, and is frequently co-expressed with ER-α. Early phase studies on WT1 vaccine in gynecological cancers are ongoing. In this study we aimed to determine the prognostic value of WT1 in high-grade serous ovarian carcinoma. METHODS: WT1 protein expression was determined by immunohistochemistry in a cohort of 207 primary high-grade serous ovarian carcinomas...
March 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/26690485/dendritic-cell-based-adjuvant-vaccination-targeting-wilms-tumor-1-in-patients-with-advanced-colorectal-cancer
#14
Shigetaka Shimodaira, Kenji Sano, Koichi Hirabayashi, Terutsugu Koya, Yumiko Higuchi, Yumiko Mizuno, Naoko Yamaoka, Miki Yuzawa, Takashi Kobayashi, Kenichi Ito, Tomonobu Koizumi
Despite significant recent advances in the development of immune checkpoint inhibitors, the treatment of advanced colorectal cancer involving metastasis to distant organs remains challenging. We conducted a phase I study to investigate the safety and immunogenicity of Wilms' tumor (WT1) class I/II peptides-pulsed dendritic cell DC vaccination for patients with advanced colorectal cancer. Standard treatment comprising surgical resection and chemotherapy was followed by one course of seven biweekly administrations of 1-2 × 10⁷ DCs with 1-2 KE of OK-432 (streptococcal preparation) in three patients...
2015: Vaccines
https://www.readbyqxmd.com/read/26519872/immune-responses-to-wt1-in-patients-with-aml-or-mds-after-chemotherapy-and-allogeneic-stem-cell-transplantation
#15
Rosaely Casalegno-Garduño, Anita Schmitt, Alf Spitschak, Jochen Greiner, Lei Wang, Inken Hilgendorf, Carsten Hirt, Anthony D Ho, Mathias Freund, Michael Schmitt
Wilms' tumor gene 1 (WT1) is overexpressed in leukemia and WT1-derived CD8(+) T-cell epitopes for immunotherapies targeting WT1 have been defined. Here, we analyzed expression of WT1 in 226 peripheral blood and bone marrow samples from patients with acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) before and after allogeneic stem cell transplantation (SCT). Transcripts were assessed by quantitative polymerase chain reaction, and WT1-specific CD8+ cytotoxic T cells (CTL) were monitored by tetramer staining and enzyme-linked immunospot (ELISPOT) assays...
April 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/26494971/prognostic-significance-of-plasma-interleukin-6-8-in-pancreatic-cancer-patients-receiving-chemoimmunotherapy
#16
Shintaro Tsukinaga, Mikio Kajihara, Kazuki Takakura, Zensho Ito, Tomoya Kanai, Keisuke Saito, Shinichiro Takami, Hiroko Kobayashi, Yoshihiro Matsumoto, Shunichi Odahara, Kan Uchiyama, Hiroshi Arakawa, Masato Okamoto, Haruo Sugiyama, Kazuki Sumiyama, Toshifumi Ohkusa, Shigeo Koido
AIM: To investigate the association of plasma levels of interleukin (IL)-6 and -8 with Wilms' tumor 1 (WT1)-specific immune responses and clinical outcomes in patients with pancreatic ductal adenocarcinoma (PDA) treated with dendritic cells (DCs) pulsed with three types of major histocompatibility complex class I and II-restricted WT1 peptides combined with chemotherapy. METHODS: During the entire treatment period, plasma levels of IL-6 and -8 were analyzed by ELISA...
October 21, 2015: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/26469989/feasibility-of-cancer-immunotherapy-with-wt1-peptide-vaccination-for-solid-and-hematological-malignancies-in-children
#17
Akihisa Sawada, Masami Inoue, Osamu Kondo, Kayo Yamada-Nakata, Takashi Ishihara, Yuko Kuwae, Masanori Nishikawa, Yasuhiro Ammori, Akihiro Tsuboi, Yusuke Oji, Maho Koyama-Sato, Yoshihiro Oka, Masahiro Yasui, Haruo Sugiyama, Keisei Kawa
BACKGROUND: Advances in cancer immunotherapy in the pediatric field are needed in order to improve the prognosis of children with malignancies. We conducted a prospective phase I/II study of WT1 peptide vaccination for children with relapsed or refractory malignancies. METHODS: The main eligibility criteria were affected tissues or leukemic cells expressing the WT1 gene, and patients (and donors for allogeneic hematopoietic stem cell transplantation) having HLA-A*24:02...
February 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/26451309/generation-of-a-cord-blood-derived-wilms-tumor-1-dendritic-cell-vaccine-for-aml-patients-treated-with-allogeneic-cord-blood-transplantation
#18
Colin de Haar, Maud Plantinga, Nina Jg Blokland, Niek P van Til, Thijs Wh Flinsenberg, Viggo F Van Tendeloo, Evelien L Smits, Louis Boon, Lotte Spel, Marianne Boes, Jaap Jan Boelens, Stefan Nierkens
The poor survival rates of refractory/relapsed acute myeloid leukemia (AML) patients after haematopoietic cell transplantation (HCT) requires the development of additional immune therapeutic strategies. As the elicitation of tumor-antigen specific cytotoxic T lymphocytes (CTLs) is associated with reduced relapses and enhanced survival, enhanced priming of these CTLs using an anti-AML vaccine may result in long-term immunity against AML. Cord blood (CB), as allogeneic HCT source, may provide a unique setting for such post-HCT vaccination, considering its enhanced graft-versus-leukemia (GvL) effects and population of highly responsive naïve T cells...
November 2015: Oncoimmunology
https://www.readbyqxmd.com/read/26389576/therapeutic-bispecific-t-cell-engager-antibody-targeting-the-intracellular-oncoprotein-wt1
#19
Tao Dao, Dmitry Pankov, Andrew Scott, Tatyana Korontsvit, Victoriya Zakhaleva, Yiyang Xu, Jingyi Xiang, Su Yan, Manuel Direito de Morais Guerreiro, Nicholas Veomett, Leonid Dubrovsky, Michael Curcio, Ekaterina Doubrovina, Vladimir Ponomarev, Cheng Liu, Richard J O'Reilly, David A Scheinberg
Intracellular tumor antigens presented on the cell surface in the context of human leukocyte antigen (HLA) molecules have been targeted by T cell-based therapies, but there has been little progress in developing small-molecule drugs or antibodies directed to these antigens. Here we describe a bispecific T-cell engager (BiTE) antibody derived from a T-cell receptor (TCR)-mimic monoclonal antibody (mAb) ESK1, which binds a peptide derived from the intracellular oncoprotein WT1 presented on HLA-A*02:01. Despite the very low density of the complexes at the cell surface, ESK1-BiTE selectively activated and induced proliferation of cytolytic human T cells that killed cells from multiple leukemias and solid tumors in vitro and in mice...
October 2015: Nature Biotechnology
https://www.readbyqxmd.com/read/26252465/dendritic-cell-based-immunotherapy-targeting-wilms-tumor-1-in-patients-with-recurrent-malignant-glioma
#20
Keiichi Sakai, Shigetaka Shimodaira, Shinya Maejima, Nobuyuki Udagawa, Kenji Sano, Yumiko Higuchi, Terutsugu Koya, Takanaga Ochiai, Masanori Koide, Shunsuke Uehara, Midori Nakamura, Haruo Sugiyama, Yoshikazu Yonemitsu, Masato Okamoto, Kazuhiro Hongo
OBJECT: Dendritic cell (DC)-based vaccination is considered a potentially effective therapy against advanced cancer. The authors conducted a Phase I study to investigate the safety and immunomonitoring of Wilms' tumor 1 (WT1)-pulsed DC vaccination therapy for patients with relapsed malignant glioma. METHODS: WT1-pulsed and/or autologous tumor lysate-pulsed DC vaccination therapy was performed in patients with relapsed malignant gliomas. Approximately 1 × 10(7) to 2 × 10(7) pulsed DCs loaded with WT1 peptide antigen and/or tumor lysate were intradermally injected into the axillary areas with OK-432, a streptococcal preparation, at 2-week intervals for at least 5-7 sessions (1 course) during an individual chemotherapy regimen...
October 2015: Journal of Neurosurgery
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