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Tumor specific antigens

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https://www.readbyqxmd.com/read/28346400/t-lymphocyte-homing-an-underappreciated-yet-critical-hurdle-for-successful-cancer-immunotherapy
#1
Robert Sackstein, Tobias Schatton, Steven R Barthel
Advances in cancer immunotherapy have offered new hope for patients with metastatic disease. This unfolding success story has been exemplified by a growing arsenal of novel immunotherapeutics, including blocking antibodies targeting immune checkpoint pathways, cancer vaccines, and adoptive cell therapy (ACT). Nonetheless, clinical benefit remains highly variable and patient-specific, in part, because all immunotherapeutic regimens vitally hinge on the capacity of endogenous and/or adoptively transferred T-effector (Teff) cells, including chimeric antigen receptor (CAR) T cells, to home efficiently into tumor target tissue...
March 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28345023/enhancement-of-psma-directed-car-adoptive-immunotherapy-by-pd-1-pd-l1-blockade
#2
Inna Serganova, Ekaterina Moroz, Ivan Cohen, Maxim Moroz, Mayuresh Mane, Juan Zurita, Larissa Shenker, Vladimir Ponomarev, Ronald Blasberg
Chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies has shown remarkable responses, but the same level of success has not been observed in solid tumors. A new prostate cancer model (Myc-CaP:PSMA(+)) and a second-generation anti-hPSMA human CAR T cells expressing a Click Beetle Red luciferase reporter) were used to study hPSMA targeting and assess CAR T cell trafficking and persistence by bioluminescence imaging (BLI). We investigated the antitumor efficacy of human CAR T cells targeting human prostate-specific membrane antigen (hPSMA), in the presence and absence of the target antigen; first alone and then combined with a monoclonal antibody targeting the human programmed death receptor 1 (anti-hPD1 mAb)...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28344889/loss-of-tapasin-in-human-lung-and-colon-cancer-cells-and-escape-from-tumor-associated-antigen-specific-ctl-recognition
#3
Yosuke Shionoya, Takayuki Kanaseki, Sho Miyamoto, Serina Tokita, Ayumi Hongo, Yasuhiro Kikuchi, Vitaly Kochin, Kazue Watanabe, Ryota Horibe, Hiroshi Saijo, Tomohide Tsukahara, Yoshihiko Hirohashi, Hiroki Takahashi, Noriyuki Sato, Toshihiko Torigoe
Cytotoxic T-lymphocytes (CTLs) lyse target cells after recognizing the complexes of peptides and MHC class I molecules (pMHC I) on cell surfaces. Tapasin is an essential component of the peptide-loading complex (PLC) and its absence influences the surface repertoire of MHC class I peptides. In the present study, we assessed tapasin expression in 85 primary tumor lesions of non-small cell lung cancer (NSCLC) patients, demonstrating that tapasin expression positively correlated with patient survival. CD8(+) T-cell infiltration of tumor lesions was synergistically observed with tapasin expression and correlated positively with survival...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344884/the-differentiation-and-plasticity-of-tc17-cells-are-regulated-by-ctla-4-mediated-effects-on-stats
#4
Aditya Arra, Holger Lingel, Benno Kuropka, Jonas Pick, Tina Schnoeder, Thomas Fischer, Christian Freund, Mandy Pierau, Monika C Brunner-Weinzierl
As the blockade of inhibitory surface-molecules such as CTLA-4 on T cells has led to recent advances in antitumor immune therapy, there is great interest in identifying novel mechanisms of action of CD8(+) T cells to evoke effective cytotoxic antitumor responses. Using in vitro and in vivo models, we investigated the molecular pathways underlying the CTLA-4-mediated differentiation of IL-17-producing CD8(+) T cells (Tc17 cells) that strongly impairs cytotoxicity. Our studies demonstrate that Tc17 cells lacking CTLA-4 signaling have limited production of STAT3-target gene products such as IL-17, IL-21, IL-23R and RORγt...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344872/intravenously-usable-fully-serotype-3-oncolytic-adenovirus-coding-for-cd40l-as-an-enabler-of-dendritic-cell-therapy
#5
Sadia Zafar, Suvi Parviainen, Mikko Siurala, Otto Hemminki, Riikka Havunen, Siri Tähtinen, Simona Bramante, Lotta Vassilev, Hongjie Wang, Andre Lieber, Silvio Hemmi, Tanja de Gruijl, Anna Kanerva, Akseli Hemminki
Vaccination with dendritic cells (DCs), the most potent professional antigen-presenting cells in the body, is a promising approach in cancer immunotherapy. However, tumors induce immunosuppression in their microenvironment that suppresses and impairs the function of DCs. Therefore, human clinical trials with DC therapy have often been disappointing. To improve the therapeutic efficacy and to overcome the major obstacles of DC therapy, we generated a novel adenovirus, Ad3-hTERT-CMV-hCD40L, which is fully serotype 3 and expresses hCD40L for induction of antitumor immune response...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344867/cd4-and-cd8-t-cells-are-both-needed-to-induce-paraneoplastic-neurological-disease-in-a-mouse-model
#6
Christina Gebauer, Béatrice Pignolet, Lidia Yshii, Emilie Mauré, Jan Bauer, Roland Liblau
Paraneoplastic neurological disorders (PNDs) are rare human autoimmune diseases that mostly affect the central nervous system (CNS). They are triggered by an efficient immune response against a neural self-antigen that is ectopically expressed in neoplastic tumors. Due to this shared antigenic expression, the immune system reacts not only to tumor cells but also to neural cells resulting in neurological damage. Growing data point to a major role of cell-mediated immunity in PNDs associated to autoantibodies against intracellular proteins...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344864/an-immunogenic-wt1-derived-peptide-that-induces-t-cell-response-in-the-context-of-hla-a-02-01-and-hla-a-24-02-molecules
#7
Tao Dao, Tatyana Korontsvit, Victoria Zakhaleva, Casey Jarvis, Patrizia Mondello, Claire Oh, David A Scheinberg
The Wilms' tumor oncogene protein (WT1) is a highly validated tumor antigen for immunotherapy. WT1-targeted immunotherapy has been extensively explored in multiple human trials in various cancers. However, clinical investigations using WT1 epitopes have generally focused on two peptides, HLA-restricted to HLA-A*02:01 or HLA-A*24:02. The goal of this study was to identify new epitopes derived from WT1, to expand the potential use of WT1 as a target of immunotherapy. Using computer-based MHC-binding algorithms and in vitro validation of the T cell responses specific for the identified peptides, we found that a recently identified HLA-A*24:02-binding epitope (239-247), NQMNLGATL (NQM), was also a strong CD8(+) T cell epitope for HLA-A*02:01 molecule...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344859/hla-class-ii-antigen-processing-pathway-in-tumors-molecular-defects-and-clinical-relevance
#8
REVIEW
Barbara Seliger, Matthias Kloor, Soldano Ferrone
The human leukocyte antigen (HLA) class II antigen-processing machinery (APM) presents to cognate CD4(+) T-cells antigenic peptides mainly generated from exogeneous proteins in the endocytic compartment. These CD4(+) T cells exert helper function, but may also act as effector cells, thereby recognizing HLA class II antigen-expressing tumor cells. Thus, HLA class II antigen expression by tumor cells influences the tumor antigen (TA)-specific immune responses and, depending on the cancer type, the clinical course of the disease...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344808/safety-tumor-trafficking-and-immunogenicity-of-chimeric-antigen-receptor-car-t-cells-specific-for-tag-72-in-colorectal-cancer
#9
Kristen M Hege, Emily K Bergsland, George A Fisher, John J Nemunaitis, Robert S Warren, James G McArthur, Andy A Lin, Jeffrey Schlom, Carl H June, Stephen A Sherwin
BACKGROUND: T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s. METHODS: Patients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28344660/predictive-biomarkers-and-effectiveness-of-muc1-targeted-dendritic-cell-based-vaccine-in-patients-with-refractory-non-small-cell-lung-cancer
#10
Koji Teramoto, Yoshitomo Ozaki, Jun Hanaoka, Satoru Sawai, Noriaki Tezuka, Shozo Fujino, Yataro Daigo, Keiichi Kontani
BACKGROUND: The dendritic cell (DC)-based vaccine targeting the highly immunogenic tumor antigen, MUC1, has been promising for a cancer immunotherapy; however, predictive biomarkers for beneficial clinical responses of the vaccine remain to be determined. METHODS: DCs loaded with MUC1-derived peptide were subcutaneously administered to patients with MUC1-positive non-small cell lung cancer (NSCLC) that was refractory to standard anticancer therapies, every 2 weeks...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28343345/assessment-of-nucleosides-as-putative-tumor-biomarkers-in-prostate-cancer-screening-by-ce-uv
#11
Adriana Zardini Buzatto, Mariana de Oliveira Silva, Ronei Jesus Poppi, Ana Valéria Colnaghi Simionato
Cancer is responsible for millions of deaths worldwide, but most base diseases may be cured if detected early. Screening tests may be used to identify early-stage malignant neoplasms. However, the major screening tool for prostate cancer, the prostate-specific antigen test, has unsuitable sensitivity. Since cancer cells may affect the pattern of consumption and excretion of nucleosides, such biomolecules are putative biomarkers that can be used for diagnosis and treatment evaluation. Using a previously validated method for the analysis of nucleosides in blood serum by capillary electrophoresis with UV-vis spectroscopy detection, we investigated 60 samples from healthy individuals and 42 samples from prostate cancer patients...
March 25, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28341563/avoidance-of-on-target-off-tumor-activation-using-a-co-stimulation-only-chimeric-antigen-receptor
#12
Jonathan Fisher, Pierre Abramowski, Nisansala Dilrukshi Wisidagamage Don, Barry Flutter, Anna Capsomidis, Gordon Weng-Kit Cheung, Kenth Gustafsson, John Anderson
Chimeric antigen receptors (CARs) combine T cell activation with antibody-mediated tumor antigen specificity, bypassing the need for T cell receptor (TCR) ligation. A limitation of CAR technology is on-target off-tumor toxicity caused by target antigen expression on normal cells. Using GD2 as a model cancer antigen, we hypothesized that this could be minimized by using T cells expressing Vγ9Vδ2 TCR, which recognizes transformed cells in a major histocompatibility complex (MHC)-unrestricted manner, in combination with a co-stimulatory CAR that would function independently of the TCR...
March 21, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28340171/immunohistochemical-approach-to-the-differential-diagnosis-of-meningiomas-and-their-mimics
#13
Camille Boulagnon-Rombi, Clémence Fleury, Caroline Fichel, Sophie Lefour, Aude Marchal Bressenot, Guillaume Gauchotte
The differential diagnosis between meningioma and others tumors can be challenging. This study aimed to evaluate different immunohistochemical markers for the differential diagnosis between meningioma and their morphological mimics. Immunohistochemistry was performed on tissue microarray with antiepithelial membrane antigen (EMA), progesterone receptor, somatostatin receptor 2A (SSTR2A), CD34, STAT6, S100, SOX10, HMB45, MelanA, GFAP, inhibin, and BCL2 antibodies. One hundred and twenty-seven meningiomas, 26 solitary fibrous tumor/hemangiopericytomas (SFT/HPC), 39 schwannomas, 17 hemangioblastomas, 21 melanomas, 9 gliosarcomas, 5 neurofibromas, 9 peripheral primitive neuroectodermal tumors, 7 synovial sarcomas, and 5 malignant peripheral nerve sheath tumors were included in the microarray...
March 14, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28338640/metal-based-psma-radioligands
#14
REVIEW
Eleni Gourni, Gjermund Henriksen
Prostate cancer is one of the most common malignancies for which great progress has been made in identifying appropriate molecular targets that would enable efficient in vivo targeting for imaging and therapy. The type II integral membrane protein, prostate specific membrane antigen (PSMA) is overexpressed on prostate cancer cells in proportion to the stage and grade of the tumor progression, especially in androgen-independent, advanced and metastatic disease, rendering it a promising diagnostic and/or therapeutic target...
March 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28338507/ny-eso-1-protein-cancer-vaccine-with-poly-iclc-and-ok-432-rapid-and-strong-induction-of-ny-eso-1-specific-immune-responses-by-poly-iclc
#15
Tomohira Takeoka, Hirotsugu Nagase, Koji Kurose, Yoshihiro Ohue, Makoto Yamasaki, Shuji Takiguchi, Eiichi Sato, Midori Isobe, Takayuki Kanazawa, Mitsunobu Matsumoto, Kota Iwahori, Atsunari Kawashima, Akiko Morimoto-Okazawa, Hiroyoshi Nishikawa, Mikio Oka, Linda Pan, Ralph Venhaus, Eiichi Nakayama, Masaki Mori, Yuichiro Doki, Hisashi Wada
We conducted a clinical trial of a cancer vaccine using NY-ESO-1 protein with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) and/or OK-432 against solid tumors. A total of 15 patients were sequentially enrolled in 4 cohorts. Patients in cohort 1 received NY-ESO-1 protein; cohort 2a received NY-ESO-1 protein+OK-432; cohort 2b received NY-ESO-1 protein+poly-ICLC; cohort 3 received NY-ESO-1 protein+OK-432+poly-ICLC with Montanide ISA-51. The endpoints of this trial were safety, NY-ESO-1 immune responses, and clinical response...
March 23, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28338481/clinical-use-and-optimal-cutoff-value-of-ca15-3-in-evaluation-of-adnexal-mass-retrospective-cohort-study-and-review-of-the-literature
#16
Lena Sagi-Dain, Ofer Lavie, Ron Auslander, Shlomi Sagi
OBJECTIVE: To estimate the diagnostic performance and reference values of serum cancer antigen (Ca)15-3 levels in the triage of adnexal masses. MATERIALS AND METHODS: This retrospective cohort study was carried out in 481 patients referred to the Gynecology Department at Carmel Medical Center due to adnexal mass between years 2005 and 2012. All patients underwent surgery with histopathologically confirmed diagnosis and routine preoperative measurements of serum Ca125 and Ca15-3...
March 23, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28337749/branched-i%C3%A2-antigens-on-leukemia-cells-enhanced-sensitivity-against-natural-killer-cell-cytotoxicity-through-affecting-the-target-effector-interaction
#17
Yen-Hua Lee, Yi-Jen Liao, Chin-Han Huang, Fu-Ling Chang, Ting-Hsi Fan, Yuh-Ching Twu
BACKGROUND: The aberrant glycosylation on proteins and lipids has been implicated in malignant transformations for promoting the tumorigenesis, metastasis, and evasion from the host immunity. The I-branching β-1,6-N-acetylglucosaminyltransferase, converting the straight i to branched I histo-blood group antigens, reportedly could influence the migration, invasion, and metastasis of solid tumors. STUDY DESIGN AND METHODS: We first chose the highly cytotoxic natural killer (NK)-92MI cells as effector against leukemia for this cell line has been used in several clinical trials...
March 24, 2017: Transfusion
https://www.readbyqxmd.com/read/28337641/inhibition-of-proliferation-of-prostate-cancer-cell-line-du-145-in-vitro-and-in-vivo-using-salvia-miltiorrhiza-bunge
#18
Woong Jin Bae, Jin Bong Choi, Kang Sup Kim, U Syn Ha, Sung Hoo Hong, Ji Youl Lee, Tae-Kon Hwang, Sung Yeoun Hwang, Zhi-Ping Wang, Sae Woong Kim
OBJECTIVE: To investigate the antiproliferative activity of Salvia miltiorrhiza Bunge. (SM) on the castration-resistant prostate cancer (CRPC) cell line DU-145, in vitro and in vivo. METHODS: Prostate cancer cell line (DU-145) and normal prostate cell line (RWPE-1) were treated with SM at different concentrations (3.125, 12.5, 25 and 50 μg/mL) to investigate the antiproliferative effects. DNA laddering analysis was performed to investigate the apoptosis of DU-145 cells...
March 23, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28337438/mage-a-antigens-and-cancer-immunotherapy
#19
Paul Zajac, Elke Schultz-Thater, Luigi Tornillo, Charlotte Sadowski, Emanuele Trella, Chantal Mengus, Giandomenica Iezzi, Giulio C Spagnoli
MAGE-A antigens are expressed in a variety of cancers of diverse histological origin and germinal cells. Due to their relatively high tumor specificity, they represent attractive targets for active specific and adoptive cancer immunotherapies. Here, we (i) review past and ongoing clinical studies targeting these antigens, (ii) analyze advantages and disadvantages of different therapeutic approaches, and (iii) discuss possible improvements in MAGE-A-specific immunotherapies.
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28337274/decitabine-treatment-sensitizes-tumor-cells-to-t-cell-mediated-cytotoxicity-in-patients-with-myelodysplastic-syndromes
#20
Zheng Zhang, Qi He, Ying Tao, Juan Guo, Feng Xu, Ling-Yun Wu, You-Shan Zhao, Dong Wu, Li-Yu Zhou, Ji-Ying Su, Lu-Xi Song, Chao Xiao, Xiao Li, Chun-Kang Chang
Decitabine treatment improves immunological recognition that increases expression of cancer-testis antigens (CTAs) against solid tumors. The mechanisms of decitabine enhancement of immunogenicity when used for patients with myelodysplastic syndromes (MDS) remain unclear. In the present study, we found relatively low baseline expression of MAGE-A1, MAGE-A3, and SP17 in MDS-derived cell lines. Decitabine treatment significantly improved MAGE-A1, MAGE-A3, and SP17 expression in these cell lines and in MDS patients...
2017: American Journal of Translational Research
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