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https://www.readbyqxmd.com/read/29531227/divergent-t-cell-receptor-recognition-modes-of-a-hla-i-restricted-extended-tumour-associated-peptide
#1
Kok Fei Chan, Benjamin S Gully, Stephanie Gras, Dennis X Beringer, Lars Kjer-Nielsen, Jonathan Cebon, James McCluskey, Weisan Chen, Jamie Rossjohn
Human leukocyte antigen (HLA)-I molecules generally bind short peptides (8-10 amino acids), although extended HLA-I restricted peptides (>10 amino acids) can be presented to T cells. However, the function of such extended HLA-I epitopes in tumour immunity, and how they would be recognised by T-cell receptors (TCR) remains unclear. Here we show that the structures of two distinct TCRs (TRAV4+ TRAJ21+ -TRBV28+ TRBJ2-3+ and TRAV4+ TRAJ8+ -TRBV9+ TRBJ2-1+ ), originating from a polyclonal T-cell repertoire, bind to HLA-B*07:02, presenting a 13-amino-acid-long tumour-associated peptide, NY-ESO-160-72 ...
March 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29515077/-cancer-immunotherapy-using-gene-engineered-t-cells
#2
Shinichi Kageyama
Cancer immunotherapies using gene-engineered T cells comprise adoptive transfer of T-cell receptor (TCR) and chimeric antigen receptor (CAR) gene-transduced T cells. Although CD19-targeting CAR-T cell therapy is the most progressed, wherein B-cell malignancy is treated efficiently, it also induces cytokine release syndrome and neurotoxicity, which frequently leads to serious adverse events. Of note, TCR-T cell therapy has been primarily used to target melanoma, resulting in 30%-50% of tumor responses. In clinical trials that target NY-ESO-1-expressing synovial sarcoma, a high efficacy of 50%-60% has been obtained...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29493121/endolysosomal-escape-nanovaccines-through-adjuvant-induced-tumor-antigen-assembly-for-enhanced-effector-cd8-t-cell-activation
#3
Liping Qiu, Michael Valente, Yusuf Dolen, Eliezer Jäger, Martin Ter Beest, Liyan Zheng, Carl G Figdor, Martijn Verdoes
The activation of tumor-specific effector immune cells is key for successful immunotherapy and vaccination is a powerful strategy to induce such adaptive immune responses. However, the generation of effective anticancer vaccines is challenging. To overcome these challenges, a novel straight-forward strategy of adjuvant-induced tumor antigen assembly to generate nanovaccines with superior antigen/adjuvant loading efficiency is developed. To protect nanovaccines in circulation and to introduce additional functionalities, a biocompatible polyphenol coating is installed...
March 1, 2018: Small
https://www.readbyqxmd.com/read/29480665/akap4-spag9-and-ny-eso-1-in-iranian-colorectal-cancer-patients-as-probable-diagnostic-and-prognostic-biomarkers
#4
Ameneh Tavakoli Koudehi, Bahar Mahjoubi, Rezvan Mirzaei, Samira Shabani, Frouzandeh Mahjoubi
Background and objectives: Colorectal cancer (CRC) is the most common gastrointestinal cancer and the second leading cause of cancer death in women in the world. Cancer-Testis Antigens (CTAs) are a group of tumor-associated proteins which typically are expressed in normal reproductive cells of men, but their expression in normal somatic cells is silenced. CTAs, due to their limited expression pattern, are considered as promising targets for cancer diagnosis and immuno-therapy. Methods: Expression of AKAP4, SPAG9 and CTAG1B genes from the CTAs family was studied in both tumor and normal tissues of 62 Iranian CRC patients by RT-PCR with the aim of finding biomarkers for early detection and anticipated progression...
February 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29465777/expression-of-mage-a-and-ny-eso-1-cancer-testis-antigens-is-enriched-in-triple-negative-invasive-breast-cancers
#5
Ashwini Raghavendra, Priyakshi Kalita-de Croft, Ana Cristina Vargas, Chanel E Smart, Peter T Simpson, Jodi M Saunus, Sunil R Lakhani
AIMS: A better understanding of the expression of cancer testis antigens (CTA) in breast cancer might identify new immunotherapy options, especially for triple-negative (TN) tumours, which lack expression of conventional therapeutic targets ER, PR and HER2 (receptors for Oestrogen, Progesterone and Human epidermal growth factor). The aim of this study was to quantify the expression of MAGE-A and NY-ESO-1 CTAs in breast cancer, and relate this to known clinicopathologic parameters. METHODS AND RESULTS: We surveyed MAGE-A and NY-ESO-1 protein expression in an unselected cohort of 367 breast tumours (out of which 65 tumours were TN), with accompanying clinical follow-up data, using immunohistochemistry (IHC) analysis of tissue microarrays...
February 21, 2018: Histopathology
https://www.readbyqxmd.com/read/29399408/oncolytic-viruses-sensitize-human-tumor-cells-for-ny-eso-1-tumor-antigen-recognition-by-cd4-effector-t-cells
#6
Tiphaine Delaunay, Mathilde Violland, Nicolas Boisgerault, Soizic Dutoit, Virginie Vignard, Christian Münz, Monique Gannage, Brigitte Dréno, Kristine Vaivode, Dace Pjanova, Nathalie Labarrière, Yaohe Wang, E Antonio Chiocca, Fabrice Le Boeuf, John C Bell, Philippe Erbs, Frédéric Tangy, Marc Grégoire, Jean-François Fonteneau
Oncolytic immunotherapy using oncolytic viruses (OV) has been shown to stimulate the antitumor immune response by inducing the release of tumor-associated antigens (TAA) and danger signals from the dying infected tumor cells. In this study, we sought to determine if the lysis of tumor cells induced by different OV: measles virus, vaccinia virus, vesicular stomatitis virus, herpes simplex type I virus, adenovirus or enterovirus, has consequences on the capacity of tumor cells to present TAA, such as NY-ESO-1...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399140/cancer-testis-antigens-are-predominantly-expressed-in-uterine-leiomyosarcoma-compared-with-non-uterine-leiomyosarcoma
#7
Kunio Iura, Kenichi Kohashi, Nobuko Yasutake, Takeaki Ishii, Akira Maekawa, Hirofumi Bekki, Hiroshi Otsuka, Yuichi Yamada, Hidetaka Yamamoto, Yoshihiro Ohishi, Yoshihiro Matsumoto, Yukihide Iwamoto, Yoshinao Oda
Leiomyosarcomas account for ~24% of all adult sarcomas, and develop predominantly either in the uterus [uterine leiomyosarcoma (ULMS)] or in deep soft tissue or the retroperitoneum [non-uterine leiomyosarcoma (NULMS)]. Leiomyosarcomas are relatively chemoresistant tumors, and the prognosis of patients with leiomyosarcomas is poor. Cancer-testis (CT) antigens are considered promising immunotherapeutic targets because of their restricted expression in normal tissue, except in the testis. Little is known about the expression of CT antigens in leiomyosarcomas...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29371783/evaluation-of-a-serum-lung-cancer-biomarker-panel
#8
Peter J Mazzone, Xiao-Feng Wang, Xiaozhen Han, Humberto Choi, Meredith Seeley, Richard Scherer, Victoria Doseeva
Background: A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact of combining molecular and clinical variables. Methods: The training set of serum samples was purchased from commercially available biorepositories. The testing set was from a biorepository at the Cleveland Clinic...
2018: Biomarker Insights
https://www.readbyqxmd.com/read/29306769/phase-ii-trial-of-ipilimumab-in-melanoma-patients-with-preexisting-humoural-immune-response-to-ny-eso-1
#9
G M Haag, I Zoernig, J C Hassel, N Halama, J Dick, N Lang, L Podola, J Funk, C Ziegelmeier, S Juenger, M Bucur, L Umansky, C S Falk, A Freitag, I Karapanagiotou-Schenkel, P Beckhove, A Enk, D Jaeger
BACKGROUND: Immune checkpoint therapy has dramatically changed treatment options in patients with metastatic melanoma. However, a relevant part of patients still does not respond to treatment. Data regarding the prognostic or predictive significance of preexisting immune responses against tumour antigens are conflicting. Retrospective data suggested a higher clinical benefit of ipilimumab in melanoma patients with preexisting NY-ESO-1-specific immunity. PATIENTS AND METHODS: Twenty-five patients with previously untreated or treated metastatic melanoma and preexisting humoural immune response against NY-ESO-1 received ipilimumab at a dose of 10 mg/kg in week 1, 4, 7, 10 followed by 3-month maintenance treatment for a maximum of 48 weeks...
February 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29290656/early-gastric-cancer-frequently-has-high-expression-of-kk-lc-1-a-cancer-testis-antigen
#10
Nobue Futawatari, Takashi Fukuyama, Rui Yamamura, Akiko Shida, Yoshihito Takahashi, Yatsushi Nishi, Yoshinobu Ichiki, Noritada Kobayashi, Hitoshi Yamazaki, Masahiko Watanabe
AIM: To assess cancer-testis antigens (CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors. METHODS: Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1 (KK-LC-1), melanoma antigen (MAGE)-A1, MAGE-A3 and New York esophageal cancer-1 (NY-ESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained...
December 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29284705/immunotherapy-of-myelodysplastic-syndrome-you-can-run-but-you-can-t-hide
#11
Ephraim Joseph Fuchs
The hypomethylating agent decitabine induces expression of the cancer/testis antigen NY-ESO-1 in the myeloid cells of patients with myelodysplastic syndrome (MDS). Patients with MDS treated with decitabine and an NY-ESO-1 vaccine developed NY-ESO-1-specific T-cell responses directed against their abnormal myeloid cells, raising hopes for combinatorial immunotherapy of this disease. Clin Cancer Res; 24(5); 991-3. ©2017 AACR See related article by Griffiths et al., p. 1019 .
March 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29280411/the-potential-of-the-cmb305-vaccine-regimen-to-target-ny-eso-1-and-improve-outcomes-for-synovial-sarcoma-and-myxoid-round-cell-liposarcoma-patients
#12
Seth M Pollack
Synovial Sarcoma (SS) and Myxoid Round Cell Liposarcoma (MRCL) are devastating sarcoma subtypes with few treatment options and poor outcomes in the advanced setting. However, both these diseases may be ideal for novel immunotherapies targeting the cancer-testis antigen, NY-ESO-1. Areas covered: In this review, we discuss the novel NY-ESO-1 targeted vaccine regimen, CMB305. This regimen uses a unique integration-deficient, dendritic-cell targeting lentiviral vector from the ZVex® platform, LV305, in order to prime NY-ESO-1 specific T cells...
February 2018: Expert Review of Vaccines
https://www.readbyqxmd.com/read/29202325/co-delivery-of-human-cancer-testis-antigens-with-adjuvant-in-protein-nanoparticles-induces-higher-cell-mediated-immune-responses
#13
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...
February 2018: 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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