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https://www.readbyqxmd.com/read/29202325/co-delivery-of-human-cancer-testis-antigens-with-adjuvant-in-protein-nanoparticles-induces-higher-cell-mediated-immune-responses
#1
Medea Neek, Jo Anne Tucker, Tae Il Kim, Nicholas M Molino, Edward L Nelson, Szu-Wen Wang
Nanoparticles have attracted considerable interest as cancer vaccine delivery vehicles for inducing sufficient CD8+ T cell-mediated immune responses to overcome the low immunogenicity of the tumor microenvironment. Our studies described here are the first to examine the effects of clinically-tested human cancer-testis (CT) peptide epitopes within a synthetic nanoparticle. Specifically, we focused on two significant clinical CT targets, the HLA-A2 restricted epitopes of NY-ESO-1 and MAGE-A3, using a viral-mimetic packaging strategy...
November 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/29187853/fine-tuning-of-optimal-tcr-signaling-in-tumor-redirected-cd8-t-cells-by-distinct-tcr-affinity-mediated-mechanisms
#2
Danilo Presotto, Efe Erdes, Minh Ngoc Duong, Mathilde Allard, Pierre-Olivier Regamey, Manfredo Quadroni, Marie-Agnès Doucey, Nathalie Rufer, Michael Hebeisen
Redirecting CD8 T cell immunity with self/tumor-specific affinity-matured T cell receptors (TCRs) is a promising approach for clinical adoptive T cell therapy, with the aim to improve treatment efficacy. Despite numerous functional-based studies, little is known about the characteristics of TCR signaling (i.e., intensity, duration, and amplification) and the regulatory mechanisms underlying optimal therapeutic T cell responses. Using a panel of human SUP-T1 and primary CD8 T cells engineered with incremental affinity TCRs against the cancer-testis antigen NY-ESO-1, we found that upon activation, T cells with optimal-affinity TCRs generated intense and sustained proximal (CD3ζ, LCK) signals associated with distal (ERK1/2) amplification-gain and increased function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29181273/optimizing-peptide-epitope-based-autoantibody-detection-in-cancer-patients
#3
Maize Wang, Shirley H Lomeli, Wilbur A Franklin, Sarah Lee, Allan J Pantuck, Gang Zeng
Autoantibody (autoAb) response is an important arm of endogenously arising anti-tumor immune responses, and has received new attention as a cancer biomarker with the recent success of immune check-point inhibitor therapy. Our laboratory has been focusing on measuring autoAb against B-cell epitopes in order to bypass the necessity to purify a panel of recombinant proteins. In order to optimize peptide-based autoAb measurement and to increase sensitivities to cover more patients, we developed a new approach of using mixed peptides to conjugate on the same microsphere and compared its results with the use of a dominant peptide epitope using Luminex microbead-based multiplex assays...
2017: American Journal of Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29157306/a-pilot-study-of-the-immunogenicity-of-a-9-peptide-breast-cancer-vaccine-plus-poly-iclc-in-early-stage-breast-cancer
#4
Patrick M Dillon, Gina R Petroni, Mark E Smolkin, David R Brenin, Kimberly A Chianese-Bullock, Kelly T Smith, Walter C Olson, Ibrahim S Fanous, Carmel J Nail, Christiana M Brenin, Emily H Hall, Craig L Slingluff
BACKGROUND: Breast cancer remains a leading cause of cancer death worldwide. There is evidence that immunotherapy may play a role in the eradication of residual disease. Peptide vaccines for immunotherapy are capable of durable immune memory, but vaccines alone have shown sparse clinical activity against breast cancer to date. Toll-like receptor (TLR) agonists and helper peptides are excellent adjuvants for vaccine immunotherapy and they are examined in this human clinical trial. METHODS: A vaccine consisting of 9 MHC class I-restricted breast cancer-associated peptides (from MAGE-A1, -A3, and -A10, CEA, NY-ESO-1, and HER2 proteins) was combined with a TLR3 agonist, poly-ICLC, along with a helper peptide derived from tetanus toxoid...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29156688/frequency-of-expression-and-generation-of-t-cell-responses-against-antigens-on-multiple-myeloma-cells-in-patients-included-in-the-gmmg-mm5-trial
#5
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
Background: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. Results: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29147626/functional-t-cells-targeting-tumor-associated-antigens-are-predictive-for-recurrence-free-survival-of-patients-with-radically-operated-non-small-cell-lung-cancer
#6
Seyer Safi, Yoshikane Yamauchi, Anchana Rathinasamy, Slava Stamova, Martin Eichhorn, Arne Warth, Geraldine Rauch, Hendrik Dienemann, Hans Hoffmann, Philipp Beckhove
In this prospective study, we examined postoperative follow-up and preoperative IFN-γ T cell responses against 14 non-small cell lung cancer (NSCLC)-associated antigens in the blood of 51 patients with NSCLC, 7 patients with benign pulmonary tumors, and 10 tumor-free patients by enzyme-linked immunospot assay. The phenotype and function of T cells specific for tumor-associated antigens (TAAs) in the blood or tumor tissue of 9 NSCLC patients were characterized in detail using TNF-α, IL-2, and IFN-γ cytokine capture assays...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29094183/a-phase-i-vaccination-study-with-dendritic-cells-loaded-with-ny-eso-1-and-%C3%AE-galactosylceramide-induction-of-polyfunctional-t-cells-in-high-risk-melanoma-patients
#7
Olivier Gasser, Katrina J Sharples, Catherine Barrow, Geoffrey M Williams, Evelyn Bauer, Catherine E Wood, Brigitta Mester, Marina Dzhelali, Graham Caygill, Jeremy Jones, Colin M Hayman, Victoria A Hinder, Jerome Macapagal, Monica McCusker, Robert Weinkove, Gavin F Painter, Margaret A Brimble, Michael P Findlay, P Rod Dunbar, Ian F Hermans
Vaccines that elicit targeted tumor antigen-specific T-cell responses have the potential to be used as adjuvant therapy in patients with high risk of relapse. However, the responses induced by vaccines in cancer patients have generally been disappointing. To improve vaccine function, we investigated the possibility of exploiting the immunostimulatory capacity of type 1 Natural killer T (NKT) cells, a cell type enriched in lymphoid tissues that can trigger improved antigen-presenting function in dendritic cells (DCs)...
November 1, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29058035/ny-eso-1-and-survivin-specific-t-cell-responses-in-the-peripheral-blood-from-patients-with-glioma
#8
Zhenjiang Liu, Thomas Poiret, Oscar Persson, Qingda Meng, Lalit Rane, Jiri Bartek, Julia Karbach, Hans-Michael Altmannsberger, Christopher Illies, Xiaohua Luo, Inti Harvey-Peredo, Elke Jäger, Ernest Dodoo, Markus Maeurer
The prognosis for patients with glioblastoma is grim. Ex vivo expanded tumor-associated antigen (TAA)-reactive T-cells from patients with glioma may represent a viable source for anticancer-directed cellular therapies. Immunohistochemistry was used to test the survivin (n = 40 samples) and NY-ESO-1 (n = 38 samples) protein expression in tumor specimens. T-cells from peripheral blood were stimulated with TAAs (synthetic peptides) in IL-2 and IL-7, or using a combination of IL-2, IL-15 and IL-21. CD4(+) and CD8(+) T-cells were tested for antigen-specific proliferation by flow cytometry, and IFN-γ production was tested by ELISA...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29045966/-immune-effects-of-specific-ctls-response-induced-by-dendritic-cells-pulsed-with-ny-eso-1-peptide
#9
J W Liu, X Lu, Z M Yang, L J Deng, L Yang
OBJECTIVE: To explore the potential of autologous dendritic cells (DCs) pulsed with caner/testis antigen NY-ESO-1 peptides in inducing specific cytotoxic T lymphocyte (CTLs) response and antineoplastic immune function of specific CTLs. METHODS: Fifteen patients with II to III stage positive HLA -A0201(+) and NY-ESO-1(+) were enrolled in the Cancer Hospital Chinese Academy of Medical Sciences on the basis of preclinical experiments from November 2014 to October 2015, and their peripheral blood mononuclear cells (PBMCs) and peripheral blood lymphocytes (PBLs) were isolated...
October 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/29032737/melanoma-a-prototype-of-cancer-testis-antigen-expressing-malignancies
#10
Sepideh Faramarzi, Soudeh Ghafouri-Fard
Melanoma is the first malignancy in which expression and immunogenicity of cancer-testis antigens (CTAs) have been documented. Several CTAs have been shown to be expressed in melanoma samples especially those with metastatic potential. Many of them have been shown to exert oncogenic effects through modulation of essential pathways involved in melanoma. The crucial role of CTAs in the pathogenesis of melanoma, the high prevalence of expression of CTA panels in melanoma and the presence of spontaneous as well as inducible immune responses against CTAs in melanoma patients potentiate CTAs as immunotherapeutic targets...
October 2017: Immunotherapy
https://www.readbyqxmd.com/read/28949447/exosomal-proteins-as-prognostic-biomarkers-in-non-small-cell-lung-cancer
#11
(no author information available yet)
BACKGROUND: Use of exosomes as biomarkers in non-small cell lung cancer (NSCLC) is an intriguing approach in the liquid-biopsy era. Exosomes are nano-sized vesicles with membrane-bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection for optimal treatment. We here evaluate exosomes by protein phenotyping as a prognostic biomarker in NSCLC. METHODS: Exosomes from plasma of 276 NSCLC patients were phenotyped using the Extracellular Vesicle Array; 49 antibodies captured the proteins on the exosomes, and a cocktail of biotin-conjugated antibodies binding the general exosome markers CD9, CD81 and CD63 was used to visualise the captured exosomes...
December 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28947565/ny-eso-1-vaccination-in-combination-with-decitabine-induces-antigen-specific-t-lymphocyte-responses-in-patients-with-myelodysplastic-syndrome
#12
Elizabeth A Griffiths, Pragya Srivastava, Junko Matsuzaki, Zachary Brumberger, Eunice S Wang, Justin Kocent, Austin Miller, Gregory W Roloff, Hong Yuen Wong, Benjamin E Paluch, Linda G Lutgen-Dunckley, Brandon L Martens, Kunle Odunsi, Adam R Karpf, Christopher S Hourigan, Michael J Nemeth
PURPOSE: Treatment options are limited for patients with high-risk myelodysplastic syndrome (MDS). The azanucleosides, azacitidine and decitabine, are front-line therapy for MDS that induce promoter demethylation and gene expression of the highly immunogenic tumor antigen NY-ESO-1. We demonstrated that AML patients receiving decitabine exhibit induction of NY-ESO-1 expression in circulating blasts. We hypothesized that vaccinating against NY-ESO-1 in MDS patients receiving decitabine would capitalize upon induced NY-ESO-1 expression in malignant myeloid cells to provoke an NY-ESO-1-specific-MDS directed cytotoxic T-cell immune response...
September 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
#13
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
#14
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
#15
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
#16
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
#17
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...
September 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
#18
REVIEW
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
#19
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
#20
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
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