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NY-ESO-1

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https://www.readbyqxmd.com/read/28926357/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#1
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
September 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#2
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28891906/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#3
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
October 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28866803/personalized-ex-vivo-multiple-peptide%C3%A2-enrichment-and-detection-of-t-cells-reactive-to-multiple-tumor-associated-antigens-in-prostate-cancer-patients
#4
Pavla Taborska, Dmitry Stakheev, Zuzana Strizova, Katerina Vavrova, Michal Podrazil, Jirina Bartunkova, Daniel Smrz
Personalized peptide vaccination is a promising immunotherapeutic approach in prostate cancer (PCa). We therefore examined whether an approach, utilizing personalized multiple peptide-mediated ex vivo enrichment with effector T cells reactive to multiple tumor-associated antigens (TAAs), could be employed as a basis for the development of T cell immunotherapy of PCa. In this study, we used the non-adherent fraction (lymphocytes) of cryopreserved peripheral blood mononuclear cells from a leukapheretic product of biochemically recurrent (BR, n = 14) and metastatic hormone-refractory (HR, n = 12) PCa patients...
September 2, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28759137/soft-tissue-sarcomas-from-a-morphological-to-a-molecular-biological-approach
#5
REVIEW
Yoshinao Oda, Hidetaka Yamamoto, Kenichi Kohashi, Yuichi Yamada, Kunio Iura, Takeaki Ishii, Akira Maekawa, Hirofumi Bekki
Recently developed molecular genetic techniques have led to the elucidation of tumor-specific genomic alterations and thereby the reclassification of tumor entities of soft tissue sarcoma. A solitary fibrous tumor-mimicking tumor with the AHRR-NCOA2 gene has been isolated as angiofibroma of soft tissue. As for small round cell sarcomas, novel fusion genes such as CIC-DUX4 and BCOR-CCNB3 have been identified in these tumor groups. SMARCB1/INI1 deficient tumors with round cell morphology are also expected to be reclassified in three types, based on the combination of their morphology and genotype...
July 31, 2017: Pathology International
https://www.readbyqxmd.com/read/28750095/serum-tumor-associated-autoantibodies-as-diagnostic-biomarkers-for-lung-cancer-a-systematic-review-and-meta-analysis
#6
Zhen-Ming Tang, Zhou-Gui Ling, Chun-Mei Wang, Yan-Bin Wu, Jin-Liang Kong
OBJECTIVE: We performed a comprehensive review and meta-analysis to evaluate the diagnostic values of serum single and multiplex tumor-associated autoantibodies (TAAbs) in patients with lung cancer (LC). METHODS: We searched the MEDLINE and EMBASE databases for relevant studies investigating serum TAAbs for the diagnosis of LC. The primary outcomes included sensitivity, specificity and accuracy of the test. RESULTS: The systematic review and meta-analysis included 31 articles with single autoantibody and 39 with multiplex autoantibodies...
2017: PloS One
https://www.readbyqxmd.com/read/28716148/prevalence-of-plasma-autoantibody-against-cancer-testis-antigen-ny-eso-1-in-htlv-1-infected-individuals-with-different-clinical-status
#7
Yasuo Shiohama, Tadasuke Naito, Toshio Matsuzaki, Reiko Tanaka, Takeaki Tomoyose, Hiroshi Takashima, Takuya Fukushima, Yuetsu Tanaka, Mineki Saito
BACKGROUND: Detection of specific immune responses against cancer/testis antigen NY-ESO-1 was recently reported in patients with adult T-cell leukemia/lymphoma (ATL) and human T-cell leukemia virus type 1 (HTLV-1)-infected asymptomatic carriers (ACs). However, the relationship of the responses with the HTLV-1 proviral load (PVL) and the levels of viral gene expression remain unclear. FINDINGS: We measured plasma levels of autoantibodies to NY-ESO-1 immunogenic tumor antigen in HTLV-1-infected individuals with different clinical status, and in healthy controls...
July 17, 2017: Virology Journal
https://www.readbyqxmd.com/read/28677424/expansion-of-cancer-germline-antigen-specific-cytotoxic-t-lymphocytes-for-immunotherapy
#8
Deepa Kolaseri Krishnadas, Yali Wang, Kumaran Sundaram, Fanqi Bai, Kenneth G Lucas
The cancer germline antigens MAGE-A1, MAGE-A3, and NY-ESO-1 can be used to target relapsed or therapy-resistant malignant solid tumors, and previous studies have demonstrated that these antigens can be epigenetically upregulated on the surface of tumor cells following exposure to low-dose demethylating chemotherapy agents, such as decitabine. The extent to which cancer germline antigen cytotoxic T lymphocytes can be reliably expanded from healthy donors has not been well characterized, specifically in terms of whether these T cells consistently kill antigen-bearing targets or simply produce interferon-γ in the presence of the antigen...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28637663/ny-eso-1-tcr-single-edited-stem-and-central-memory-t-cells-to-treat-multiple-myeloma-without-graft-versus-host-disease
#9
Sara Mastaglio, Pietro Genovese, Zulma Magnani, Eliana Ruggiero, Elisa Landoni, Barbara Camisa, Giulia Schiroli, Elena Provasi, Angelo Lombardo, Andreas Reik, Nicoletta Cieri, Martina Rocchi, Giacomo Oliveira, Giulia Escobar, Monica Casucci, Bernhard Gentner, Antonello Spinelli, Anna Mondino, Attilio Bondanza, Luca Vago, Maurilio Ponzoni, Fabio Ciceri, Michael C Holmes, Luigi Naldini, Chiara Bonini
Transfer of T-cell receptors (TCRs) specific for tumor-associated antigens is a promising approach for cancer immunotherapy. We developed the TCR gene editing technology that is based on the knockout of the endogenous TCR α and β genes, followed by the introduction of tumor-specific TCR genes, and that proved safer and more effective than conventional TCR gene transfer. Although successful, complete editing requires extensive cell manipulation and 4 transduction procedures. Here we propose a novel and clinically feasible TCR "single editing" (SE) approach, based on the disruption of the endogenous TCR α chain only, followed by the transfer of genes encoding for a tumor-specific TCR...
August 3, 2017: Blood
https://www.readbyqxmd.com/read/28631119/-expression-of-cancer-testis-ct-antigens-in-pediatric-and-adolescent-melanomas
#10
REVIEW
N Behrendt, T Schultewolter, K Busam, D Frosina, G Spagnoli, A Jungbluth
BACKGROUND: One of the main problems in the diagnostics of pediatric melanomas is the differentiation from benign dermal lesions typical for this age group, such as Spitz nevus. The biological behavior of pediatric melanomas differs considerably from that of melanomas in adults. MATERIAL AND METHODS: Cancer testis (CT) antigens are named after their typical expression pattern since they are present in various types of malignant tumors but in normal adult tissues are solely expressed in testicular germ cells...
July 2017: Der Pathologe
https://www.readbyqxmd.com/read/28630212/a-pilot-study-of-stereotactic-body-radiation-therapy-combined-with-cytoreductive-nephrectomy-for-metastatic-renal-cell-carcinoma
#11
Anurag K Singh, Timothy B Winslow, Mohammad Habiby Kermany, Vincent Goritz, Lilia Heit, Austin Miller, Nicholas C Hoffend, Leighton C Stein, Lalith K Kumaraswamy, Graham W Warren, Wiam Bshara, Kunle Odunsi, Junko Matsuzaki, Scott I Abrams, Thomas Schwaab, Jason B Muhitch
Purpose: While stereotactic body radiotherapy (SBRT) can reduce tumor volumes in patients with metastatic renal cell carcinoma (mRCC), little is known regarding the immunomodulatory effects of high-dose radiation in the tumor microenvironment. The main objectives of this pilot study were to assess the safety and feasibility of nephrectomy following SBRT treatment of patients with mRCC and analyze the immunological impact of high-dose radiation.Experimental Design: Human RCC cell lines were irradiated and evaluated for immunomodulation...
September 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28628011/-criteria-for-selection-of-tumor-cells-and-prospects-for-specific-immunotherapy-for-bladder-cancer
#12
T Slavyanskaya, S -Salnikova, R Sepiashvili
Specific antitumor immunotherapy with autologous dendritic cell vaccines is one of the new approaches of modern medicine. For activation of dendritic cells highly immunogenic antigens are used, however optimal antigens in case of bladder cancer (BC) are still not researched. Cancer-testis antigens (CTA) are the most promising target in the context of creation of antitumor vaccines, because they are distinguished by pronounced immunogenicity, they are detected in different types of tumors and have limited pattern of expression in healthy tissues of grown-up organism...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28596508/promoter-hypomethylation-of-ny-eso-1-association-with-clinicopathological-features-and-pd-l1-expression-in-non-small-cell-lung-cancer
#13
Anderly C Chüeh, Mun-Sem Liew, Prudence A Russell, Marzena Walkiewicz, Aparna Jayachandran, Maud H W Starmans, Paul C Boutros, Gavin Wright, Stephen A Barnett, John M Mariadason, Thomas John
Cancer-Testis antigens (CTA) are immunogenic molecules with normal tissue expression restricted to testes but with aberrant expression in up to 30% of non-small cell lung cancers (NSCLCs). Regulation of CTA expression is mediated in part through promoter DNA methylation. Recently, immunotherapy has altered treatment paradigms in NSCLC. Given its immunogenicity and ability to be re-expressed through demethylation, NY-ESO-1 promoter methylation, protein expression and its association with programmed death receptor ligand-1 (PD-L1) expression and clinicopathological features were investigated...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588683/expression-and-immunogenicity-of-ny-eso-1-in-colorectal-cancer
#14
Ya Li, Ruifeng Song, Xinqiang Li, Feng Xu
Serum assays of NY-ESO-1 antibodies provide a guide to discriminate between patients who suffer from different types of cancer. In the present study, the expression of NY-ESO-1 was detected with the aim to identify a novel tumor antigen in colorectal cancer (CRC). Sera were obtained from 89 healthy individuals and 236 patients with CRC with stage I, II, III and IV tumors. The NY-ESO-1 autoantibody levels were determined using an enzyme-linked immunosorbent assay. The mRNA and protein expression levels of NY-ESO-1 were detected using reverse transcription-polymerase chain reaction and immunohistochemistry, respectively, in 60 CRC and paired adjacent non-tumor tissues...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28540335/ny-eso-1-expression-in-dcis-a-new-predictor-of-good-prognosis
#15
R Charles Coombes, Otavia L Caballero, Sami Shousha, Sadaf Ghaem-Maghami, Laura Woodley-Barker, Charlotte S Wilhelm-Benartzi, A Munro Neville
BACKGROUND: At present, it is difficult to predict which patients with ductal carcinoma-in-situ (DCIS) will subsequently develop frank invasive breast cancer (IDC). A recent survey by our group has shown that NY-ESO-1 and MAGEA are both expressed in DCIS. This study was aimed at determining whether expression of these antigens was related to the later development of IDC. RESULTS: 14 of 42 (33%) of patients developed invasive breast cancer during the follow up period...
March 2017: Oncoscience
https://www.readbyqxmd.com/read/28538872/melanoma-tumor-microenvironment-and-new-treatments
#16
Mara Huffenbaecher Giavina-Bianchi, Pedro Francisco Giavina-Bianchi, Cyro Festa
In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy...
March 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28536262/in-silico-and-cell-based-analyses-reveal-strong-divergence-between-prediction-and-observation-of-t-cell-recognized-tumor-antigen-t-cell-epitopes
#17
COMPARATIVE STUDY
Julien Schmidt, Philippe Guillaume, Danijel Dojcinovic, Julia Karbach, George Coukos, Immanuel Luescher
Tumor exomes provide comprehensive information on mutated, overexpressed genes and aberrant splicing, which can be exploited for personalized cancer immunotherapy. Of particular interest are mutated tumor antigen T-cell epitopes, because neoepitope-specific T cells often are tumoricidal. However, identifying tumor-specific T-cell epitopes is a major challenge. A widely used strategy relies on initial prediction of human leukocyte antigen-binding peptides by in silico algorithms, but the predictive power of this approach is unclear...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28515346/the-novel-complex-combination-of-alum-cpg-odn-and-hh2-as-adjuvant-in-cancer-vaccine-effectively-suppresses-tumor-growth-in-vivo
#18
Yaomei Tian, Meng Li, Chaoheng Yu, Rui Zhang, Xueyan Zhang, Rong Huang, Lian Lu, Fengjiao Yuan, Yingzi Fan, Bailing Zhou, Ke Men, Heng Xu, Li Yang
Single-component adjuvant is prone to eliciting a specific type of Th1 or Th2 response. So, the development of combinatorial adjuvants inducing a robust mixed Th1/Th2 response is a promising vaccination strategy against cancer. Here, we describe a novel combination of aluminum salts (alum), CpG oligodeoxynucleotide (CpG) and innate defense regulator peptide HH2 for improving anti-tumor immune responses. The CpG-HH2 complex significantly enhanced the production of IFN-γ, TNF-α and IL-1β, promoted the uptake of antigen and strengthened the activation of p38, Erk1/2 and NF-κB in vitro, compared to CpG or HH2 alone...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28438869/correlation-between-expression-of-the-cancer-testis-antigen-kk-lc-1-and-helicobacter-pylori-infection-in-gastric-cancer
#19
Takashi Fukuyama, Nobue Futawatari, Yoshinobu Ichiki, Akiko Shida, Taiga Yamazaki, Yatsushi Nishi, Hiroshi Nonoguchi, Yoshihito Takahashi, Hitoshi Yamazaki, Noritada Kobayashi
BACKGROUND/AIM: Our previous study indicated that Kita-kyushu lung cancer antigen-1 (KK-LC-1) is a cancer/testis antigen (CTA) expressed in 82% of gastric cancer cases. Here, we investigated the relationship between KK-LC-1 expression and Helicobacter pylori infection in Japanese patients with gastric cancer. PATIENTS AND METHODS: We examined CTA expression in 25 surgical gastric cancer specimens and anti-H. pylori IgGs in the serum of each patient. RESULTS: KK-LC-1 was expressed in 80% of tumor samples, markedly higher than melanoma antigen gene (MAGE)-A1, MAGE-A3, MAGE-A4, synovial sarcoma, X breakpoint 4 (SSX4) and New York esophageal squamous cell carcinoma-1 (NY-ESO-1)...
May 2017: In Vivo
https://www.readbyqxmd.com/read/28392127/ny-eso-1-expression-predicts-an-aggressive-phenotype-of-ovarian-cancer
#20
J Brian Szender, Antonios Papanicolau-Sengos, Kevin H Eng, Anthony J Miliotto, Amit A Lugade, Sacha Gnjatic, Junko Matsuzaki, Carl D Morrison, Kunle Odunsi
OBJECTIVES: NY-ESO-1 is a cancer testis antigen and a promising target for immunotherapy. The purpose of this study was to determine the expression frequency, immunogenicity, and clinical impact of NY-ESO-1 in ovarian cancer. METHODS: Immunohistochemistry (IHC), reverse-transcription polymerase chain reaction (RT-PCR), and quantitative-PCR (qRT-PCR) were utilized in an ovarian cancer (including Fallopian tube and primary peritoneal cancers) patient cohort; humoral responses against NY-ESO-1 were determined by ELISA...
June 2017: Gynecologic Oncology
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