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https://www.readbyqxmd.com/read/28651374/cd70-a-novel-target-of-car-t-cell-therapy-for-gliomas
#1
Linchun Jin, Haitao Ge, Yu Long, Changlin Yang, Yifan Emily Chang, Luyan Mu, Elias J Sayour, Gabriel De Leon, Qiong J Wang, James C Yang, Paul S Kubilis, Hongbo Bao, Songsong Xia, Dunyue Lu, Yingjun Kong, Li Hu, Yujiao Shang, Chencheng Jiang, Jing Nie, Shimin Li, Yunhe Gu, Jiahang Sun, Duane A Mitchell, Zhiguo Lin, Jianping Huang
Background: Cancer immunotherapy represents a promising treatment approach for malignant-gliomas, but is hampered by the limited number of ubiquitously expressed tumor antigens and the profoundly immunosuppressive tumor microenvironment. We identified CD70 as a novel immunosuppressive ligand and glioma target. Methods: Normal tissues derived from 52 different organs, and primary and recurrent low-grade gliomas (LGGs) and glioblastomas (GBMs) were thoroughly evaluated for CD70 gene and protein expression...
June 23, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28651074/chimeric-antigen-receptor-engineered-natural-killer-and-natural-killer-t-cells-for-cancer-immunotherapy
#2
REVIEW
Dominique Bollino, Tonya J Webb
Natural killer (NK) cells of the innate immune system and NK T (NKT) cells, which have roles in both the innate and adaptive responses, are unique lymphocyte subsets that have similarities in their functions and phenotypes. Both cell types can rapidly respond to the presence of tumor cells and participate in immune surveillance and antitumor immune responses. This has incited interest in the development of novel cancer therapeutics based on NK and NKT cell manipulation. Chimeric antigen receptors (CARs), generated through the fusion of an antigen-binding region of a monoclonal antibody or other ligand to intracellular signaling domains, can enhance lymphocyte targeting and activation toward diverse malignancies...
June 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28651018/meta-analysis-of-mirna-expression-profiles-for-prostate-cancer-recurrence-following-radical-prostatectomy
#3
Elnaz Pashaei, Elham Pashaei, Maryam Ahmady, Mustafa Ozen, Nizamettin Aydin
BACKGROUND: Prostate cancer (PCa) is a leading reason of death in men and the most diagnosed malignancies in the western countries at the present time. After radical prostatectomy (RP), nearly 30% of men develop clinical recurrence with high serum prostate-specific antigen levels. An important challenge in PCa research is to identify effective predictors of tumor recurrence. The molecular alterations in microRNAs are associated with PCa initiation and progression. Several miRNA microarray studies have been conducted in recurrence PCa, but the results vary among different studies...
2017: PloS One
https://www.readbyqxmd.com/read/28650338/ifn-%C3%AE-related-mrna-profile-predicts-clinical-response-to-pd-1-blockade
#4
Mark Ayers, Jared Lunceford, Michael Nebozhyn, Erin Murphy, Andrey Loboda, David R Kaufman, Andrew Albright, Jonathan D Cheng, S Peter Kang, Veena Shankaran, Sarina A Piha-Paul, Jennifer Yearley, Tanguy Y Seiwert, Antoni Ribas, Terrill K McClanahan
Programmed death-1-directed (PD-1-directed) immune checkpoint blockade results in durable antitumor activity in many advanced malignancies. Recent studies suggest that IFN-γ is a critical driver of programmed death ligand-1 (PD-L1) expression in cancer and host cells, and baseline intratumoral T cell infiltration may improve response likelihood to anti-PD-1 therapies, including pembrolizumab. However, whether quantifying T cell-inflamed microenvironment is a useful pan-tumor determinant of PD-1-directed therapy response has not been rigorously evaluated...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28650243/antigenicity-of-mesenchymal-stem-cells-in-an-inflamed-joint-environment
#5
Jacqueline A Hill, Jennifer M Cassano, Margaret B Goodale, Lisa A Fortier
OBJECTIVE To determine whether major histocompatability complex (MHC) class II expression in equine mesenchymal stem cells (MSCs) changes with exposure to a proinflammatory environment reflective of an inflamed joint. SAMPLE Cryopreserved bone marrow-derived MSCs from 12 horses and cartilage and synovium samples from 1 horse euthanized for reasons other than lameness. PROCEDURES In part 1 of a 3-part study, the suitability of a quantitative reverse transcriptase PCR (qRT-PCR) assay for measurement of MHC class II expression in MSCs following stimulation with interferon (IFN)-γ was assessed...
July 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28649694/immunohistochemical-expression-profiles-of-mucin-antigens-in-salivary-gland-mucoepidermoid-carcinoma-muc4-and-muc6-negative-expression-predicts-a-shortened-survival-in-the-early-postoperative-phase
#6
Kie Honjo, Tsubasa Hiraki, Michiyo Higashi, Hirotsugu Noguchi, Mitsuharu Nomoto, Takuya Yoshimura, Surinder K Batra, Suguru Yonezawa, Ichiro Semba, Norifumi Nakamura, Akihide Tanimoto, Sohsuke Yamada
In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs...
June 26, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28649380/gitr-ligand-fusion-protein-agonist-enhances-the-tumor-antigen-specific-cd8-t-cell-response-and-leads-to-long-lasting-memory
#7
Nick M Durham, Nick Holoweckyj, Randall S MacGill, Kelly McGlinchey, Ching Ching Leow, Scott H Robbins
BACKGROUND: The expansion of antigen-specific CD8 T cells is important in generating an effective and long-lasting immune response to tumors and viruses. Glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR) is a co-stimulatory receptor that binds the GITR ligand (GITRL). Agonism of GITR can produce important signals that drive expansion of effector T cell populations. METHODS: We explored two separate murine tumor models, CT26 and TC-1, for responsiveness to GITR Ligand Fusion Protein(GITRL-FP) monotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28649364/immunosurveillance-by-human-%C3%AE-%C3%AE-t-lymphocytes-the-emerging-role-of-butyrophilins
#8
REVIEW
Dieter Kabelitz, Marcus Lettau, Ottmar Janssen
In contrast to conventional T lymphocytes, which carry an αβ T-cell receptor and recognize antigens as peptides presented by major histocompatibility complex class I or class II molecules, human γδ T cells recognize different metabolites such as non-peptidic pyrophosphate molecules that are secreted by microbes or overproduced by tumor cells. Hence, γδ T cells play a role in immunosurveillance of infection and cellular transformation. Until recently, it has been unknown how the γδ T-cell receptor senses such pyrophosphates in the absence of known antigen-presenting molecules...
2017: F1000Research
https://www.readbyqxmd.com/read/28649246/redirected-primary-human-chimeric-antigen-receptor-natural-killer-cells-as-an-off-the-shelf-immunotherapy-for-improvement-in-cancer-treatment
#9
REVIEW
Olaf Oberschmidt, Stephan Kloess, Ulrike Koehl
Primary human natural killer (NK) cells recognize and subsequently eliminate virus infected cells, tumor cells, or other aberrant cells. However, cancer cells are able to develop tumor immune escape mechanisms to undermine this immune control. To overcome this obstacle, NK cells can be genetically modified to express chimeric antigen receptors (CARs) in order to improve specific recognition of cancer surface markers (e.g., CD19, CD20, and ErbB2). After target recognition, intracellular CAR domain signaling (CD3ζ, CD28, 4-1BB, and 2B4) leads to activation of PI3K or DNAX proteins (DAP10, DAP12) and finally to enhanced cytotoxicity, proliferation, and/or interferon γ release...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28649245/camelid-single-domain-antibodies-as-an-alternative-to-overcome-challenges-related-to-the-prevention-detection-and-control-of-neglected-tropical-diseases
#10
REVIEW
Carla F C Fernandes, Soraya Dos S Pereira, Marcos B Luiz, Juliana P Zuliani, Gilvan P Furtado, Rodrigo G Stabeli
Due mainly to properties such as high affinity and antigen specificity, antibodies have become important tools for biomedical research, diagnosis, and treatment of several human diseases. When the objective is to administer them for therapy, strategies are used to reduce the heterologous protein immunogenicity and to improve pharmacokinetic and pharmacodynamic characteristics. Size minimization contributes to ameliorate these characteristics, while preserving the antigen-antibody interaction site. Since the discovery that camelids produce functional antibodies devoid of light chains, studies have proposed the use of single domains for biosensors, monitoring and treatment of tumors, therapies for inflammatory and neurodegenerative diseases, drug delivery, or passive immunotherapy...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28649003/targeting-egfrviii-for-glioblastoma-multiforme
#11
Ju Yang, Jing Yan, Baorui Liu
Glioblastoma multiforme (GBM) is the most progressive primary brain tumor. Targeting a novel and highly specific tumor antigen is one of the strategies to overcome tumors. EGFR variant III (EGFRvIII) is present in 25%-33% of all patients with GBM and is exclusively expressed on tumor tissue cells. Currently, there are various approaches to target EGFRvIII, including CAR T-cell therapy, therapeutic vaccines, antibodies, and Bi-specific T Cell Engager. In this review, we focus on the preclinical and clinical findings of targeting EGFRvIII for GBM...
June 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28648976/synergistic-combination-of-murine-bone-marrow-derived-dendritic-cells-loaded-ex-vivo-with-whole-tumor-lysate-and-systemic-chemotherapy-mediates-antitumor-immune-responses-in-vivo
#12
Mohamed L Salem, Mohamed Nassef, Soha Gomaa, Ibrahim Essa
In order to get mature dendritic cells (DC) that is a crucial prerequisite for success in tumor immunotherapy protocols. Herein, we assumed that administration of murine bone marrow (BM)-derived DC (BM-DC), loaded ex vivo with whole Ehrlich ascites carcinoma (EAC) lysate, in the context of systemic chemotherapy cyclophosphamide (CTX) to induce antitumor immune responses, may be a good strategy to improve the presentation of tumor-specific antigens to the immune system. In the first series of experiments, BM cells generated either from BM of naïve mice or from BM of EAC-bearing mice were cultured in the presence of GM-CSF and IL-4 for 6days...
June 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28648905/antibodies-against-immune-checkpoint-molecules-restore-functions-of-tumor-infiltrating-t-cells-in-hepatocellular-carcinomas
#13
Guoying Zhou, Dave Sprengers, Patrick P C Boor, Michail Doukas, Hannah Schutz, Shanta Mancham, Alexander Pedroza-Gonzalez, Wojciech G Polak, Jeroen de Jonge, Marcia Gaspersz, Haidong Dong, Kris Thielemans, Qiuwei Pan, Jan N M IJzermans, Marco J Bruno, Jaap Kwekkeboom
BACKGROUND & AIMS: Ligand binding to inhibitory receptors on immune cells, such as programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA4), downregulates the T-cell-mediated immune response (called immune checkpoints). Antibodies that block these receptors increase anti-tumor immunity in patients with melanoma, non-small cell lung cancer, and renal cell cancer. Tumor-infiltrating CD4(+) and CD8(+) T cells in patients with hepatocellular carcinoma (HCC) have been found to be functionally compromised...
June 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28648732/-adoptive-transfer-of-t-lymphocytes
#14
H Vié, B Clémenceau
Within a few years, the success of treatments based on the use of T-cells armed with a chimeric T-receptor for the CD19 molecule (CAR-T CD19) has revolutionized the perception of adoptive transfer approaches. The levels of responses observed in acute leukemias, of the order of 70-90 % are indeed unprecedented. The medical and financial enthusiasm aroused by these results has led to the current situation where more than 300 clinical trials are under way, against some thirty different antigens. This enthusiasm, well justified by the first successes, must however be tempered by the difficulties associated with the use of these cells...
June 22, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/28648661/de-novo-epigenetic-programs-inhibit-pd-1-blockade-mediated-t-cell-rejuvenation
#15
Hazem E Ghoneim, Yiping Fan, Ardiana Moustaki, Hossam A Abdelsamed, Pradyot Dash, Pranay Dogra, Robert Carter, Walid Awad, Geoff Neale, Paul G Thomas, Ben Youngblood
Immune-checkpoint-blockade (ICB)-mediated rejuvenation of exhausted T cells has emerged as a promising approach for treating various cancers and chronic infections. However, T cells that become fully exhausted during prolonged antigen exposure remain refractory to ICB-mediated rejuvenation. We report that blocking de novo DNA methylation in activated CD8 T cells allows them to retain their effector functions despite chronic stimulation during a persistent viral infection. Whole-genome bisulfite sequencing of antigen-specific murine CD8 T cells at the effector and exhaustion stages of an immune response identified progressively acquired heritable de novo methylation programs that restrict T cell expansion and clonal diversity during PD-1 blockade treatment...
June 21, 2017: Cell
https://www.readbyqxmd.com/read/28648487/development-of-novel-avenues-to-overcome-challenges-facing-car-t-cells
#16
REVIEW
Soyeon Kim, Edmund K Moon
There has been dramatic success in treating patients with adoptive transfer of autologous T cells genetically modified to express a chimeric antigen receptor redirecting them to the antigen CD19. Despite this success, the application of chimeric antigen receptor T-cell therapy in solid malignancies has encountered many challenges that need to be overcome if similar success across other cancers is to become a reality. These challenges can be classified into 6 categories: the heterogeneity of tumor cell clones and tumor-associated antigen expression; poor T-cell trafficking into the tumor site; poor T-cell survival and persistence; the presence of suppressive immune cells; the secretion of suppressive soluble factors in the tumor microenvironment; and the upregulation of T-cell intrinsic inhibitory pathways...
June 10, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28648302/nephrotic-syndrome-with-cancer-immunotherapies-a-report-of-2-cases
#17
Abhijat Kitchlu, Warren Fingrut, Carmen Avila-Casado, Christopher T Chan, Michael Crump, David Hogg, Heather N Reich
Oncologic immunotherapies use a patient's immune response to eliminate tumor cells by modulation of immune checkpoints, including programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) proteins. Immune-mediated sequelae, including interstitial nephritis, have been reported; however, glomerular disease appears rare. We describe 2 cases of nephrotic syndrome in patients treated with these agents. Patient 1 received the anti-PD-1 antibody pembrolizumab for Hodgkin lymphoma. Following his second dose, he developed nephrotic syndrome and acute kidney injury...
June 22, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28647344/oncogene-expressing-senescent-melanocytes-upregulate-mhc-class-ii-a-candidate-melanoma-suppressor-function
#18
John van Tuyn, Farah Jaber-Hijazi, Douglas MacKenzie, John J Cole, Elizabeth Mann, Jeff S Pawlikowski, Taranjit Singh Rai, David M Nelson, Tony McBryan, Andre Ivanov, Karen Blyth, Hong Wu, Simon Milling, Peter D Adams
On acquisition of an oncogenic mutation, primary human and mouse cells can enter oncogene-induced senescence (OIS). OIS is characterized by a stable proliferation arrest and secretion of pro-inflammatory cytokines and chemokines, the senescence-associated secretory phenotype (SASP). Proliferation arrest and the SASP collaborate to enact tumor suppression, the former by blocking cell proliferation and the latter by recruiting immune cells to clear damaged cells. However, the interactions of OIS cells with the immune system are still poorly defined...
June 21, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28647216/characteristics-of-prostate-cancer-found-at-fifth-screening-in-the-european-randomized-study-of-screening-for-prostate-cancer-rotterdam-can-we-selectively-detect-high-grade-prostate-cancer-with-upfront-multivariable-risk-stratification-and-magnetic-resonance
#19
Arnout R Alberts, Ivo G Schoots, Leonard P Bokhorst, Frank-Jan H Drost, Geert J van Leenders, Gabriel P Krestin, Roy S Dwarkasing, Jelle O Barentsz, Fritz H Schröder, Chris H Bangma, Monique J Roobol
BACKGROUND: The harm of screening (unnecessary biopsies and overdiagnosis) generally outweighs the benefit of reducing prostate cancer (PCa) mortality in men aged ≥70 yr. Patient selection for biopsy using risk stratification and magnetic resonance imaging (MRI) may improve this benefit-to-harm ratio. OBJECTIVE: To assess the potential of a risk-based strategy including MRI to selectively identify men aged ≥70 yr with high-grade PCa. DESIGN, SETTING, AND PARTICIPANTS: Three hundred and thirty-seven men with prostate-specific antigen ≥3...
June 21, 2017: European Urology
https://www.readbyqxmd.com/read/28647208/mage-a-family-is-involved-in-gastric-cancer-progression-and-indicates-poor-prognosis-of-gastric-cancer-patients
#20
Yishui Lian, Meixiang Sang, Lina Gu, Fei Liu, Danjing Yin, Shina Liu, Weina Huang, Yanyun Wu, Baoen Shan
BACKGROUND: As the best characterized CTA family members, melanoma-associated antigens (MAGE) have been reported to express in various malignant tumors. However, the expression pattern of MAGE-A family in gastric cancer (GC) specimens and their prognostic and therapeutic significance for GC patients is still unclear. MATERIALS AND METHODS: Tissue microarray - based immunohistochemistry analysis was used to examine the expression of MAGE-A family members (including MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12) in 86 cases of GC specimens, 20 cases of the corresponding adjacent normal gastric specimens, and 9 cases of intraepithelial neoplasia specimens...
May 31, 2017: Pathology, Research and Practice
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