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Tumor specific antigens

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https://www.readbyqxmd.com/read/29234325/the-future-of-immunotherapy-a-20-year-perspective
#1
David C Wraith
Immunotherapy is the field of immunology that aims to identify treatments for diseases through induction, enhancement or suppression of an immune response. Immunotherapies designed to instigate or enhance an immune response are considered "activating immunotherapies" while those designed to repress an immune response are "suppressive immunotherapies." This perspective will focus on two areas of immunotherapy, activating immunotherapies for cancer and suppressive immunotherapies for autoimmunity both of which have seen a resurgence in interest in recent years and are likely to transform the treatment of many human diseases in the next 20 years...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29234259/simultaneous-measurements-of-follicle-stimulating-hormone-and-total-testosterone-and-associations-in-clinically-localized-prostate-cancer
#2
Antonio B Porcaro, Salvatore Siracusano, Nicolò de Luyk, Paolo Corsi, Marco Sebben, Alessandro Tafuri, Tania Processali, Davide Inverardi, Giovanni Cacciamani, Daniele Mattevi, Maria A Cerruto, Matteo Brunelli, Claudio Ghimenton, Carmelo Monaco, Walter Artibani
Objectives: To evaluate the potential relations of simultaneous measurements of basal levels of follicle stimulating hormone (FSH) and total testosterone (TT) in clinically localized prostate cancer (PCa). Materials and Methods: The study included 126 patients who had simultaneous measurements of prostate specific antigen (PSA), FSH, and TT before undergoing radical prostatectomy for clinically localized PCa. Correlations and independent associations between clinical and pathological factors were investigated by statistical methods...
November 2017: Current Urology
https://www.readbyqxmd.com/read/29233904/autologous-dendritic-cells-pulsed-with-allogeneic-tumor-cell-lysate-in-mesothelioma-from-mouse-to-human
#3
Joachim G Aerts, Pauline L de Goeje, Robin Cornelissen, Margaretha E H Kaijen-Lambers, Koen Bezemer, Cor van der Leest, Niken M Mahaweni, Andre Kunert, Ferry A L M Eskens, Cynthia Waasdorp, Eric Braakman, Bronno van der Holt, Arnold G Vulto, Rudi W Hendriks, Joost P J J Hegmans, Henk C Hoogsteden
PURPOSE: Mesothelioma has been regarded as a non-immunogenic tumor, which is also shown by the low response rates to treatments targeting the PD-1/PD-L1 axis.  Previously, we demonstrated that autologous tumor lysate-pulsed dendritic cell (DC) immunotherapy increased T-cell response towards malignant mesothelioma. However, the use of autologous tumor material hampers implementation in large clinical trials, which might be overcome by using allogeneic tumor cell lines as tumor antigen source...
December 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29228761/targeting-tumor-associated-carbohydrate-antigens-a-phase-i-study-of-a-carbohydrate-mimetic-peptide-vaccine-in-stage-iv-breast-cancer-subjects
#4
Laura F Hutchins, Issam Makhoul, Peter D Emanuel, Angela Pennisi, Eric R Siegel, Fariba Jousheghany, Xueyan Guo, Anastas D Pashov, Behjatolah Monzavi-Karbassi, Thomas Kieber-Emmons
Tumor-associated carbohydrate antigens (TACAs) support cell survival that could be interrupted by anti-TACA antibodies. Among TACAs that mediate cell survival signals are the neolactoseries antigen Lewis Y (LeY) and the ganglioside GD2. To induce sustained immunity against both LeY and GD2, we developed a carbohydrate mimicking peptide (CMP) as a surrogate pan-immunogen that mimics both. This CMP, referred to as P10s, is the N-terminal half of a peptide vaccine named P10s-PADRE, the C-terminal half of which (PADRE) is a Pan-T-cell epitope...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228650/ultrasensitive-plasma-ctdna-kras-assay-for-detection-prognosis-and-assessment-of-therapeutic-response-in-patients-with-unresectable-pancreatic-ductal-adenocarcinoma
#5
Inna Chen, Victoria M Raymond, Jennifer A Geis, Eric A Collisson, Benny V Jensen, Kirstine L Hermann, Mark G Erlander, Margaret Tempero, Julia S Johansen
Precision oncology requires sensitive and specific clinical biomarkers. Carbohydrate Antigen 19-9 (CA19-9) is widely used in pancreatic ductal adenocarcinoma (PDA) but lacks sensitivity and specificity. Nearly all PDAs harbor somatic KRAS mutations, nominating circulating tumor DNA (ctDNA) KRAS as an alternative disease biomarker, however, variable clinical performance has limited its clinical utility. We applied an ultrasensitive, PCR mutation enrichment, next generation sequencing ctDNA KRAS assay in a large cohort of patients with unresectable PDA (N = 189) recruited to the BIOPAC study between 2008-2015...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227998/the-value-of-squamous-cell-carcinoma-antigen-scca-to-determine-the-lymph-nodal-metastasis-in-cervical-cancer-a-meta-analysis-and-literature-review
#6
Ziqi Zhou, Wenbo Li, Fuquan Zhang, Ke Hu
BACKGROUND: The diagnostic power of CT or MRI on the lymph node status was limited. Supplement measurements were needed to assist the diagnosis of lymph node metastasis. The SCCa was reported to be close related to lymph node status. But currently the clinical value of serum SCCa measurement in lymph node status has not been clearly defined. This meta-analysis was to investigate this topic on a large scale. METHOD: Searching the Pubmed, Embase, Cochrane library, CNKI and Wanfang database for SCC-Ag/SCCA/SCC-antigen and cervical cancer/tumor/carcinoma/neoplasm published in any language from Jan 1 1990 to Aug 1 2017...
2017: PloS One
https://www.readbyqxmd.com/read/29227304/cell-based-immunotherapy-in-gynecologic-malignancies
#7
Bruce Schaar, Venkatesh Krishnan, Supreeti Tallapragada, Oliver Dorigo
PURPOSE OF REVIEW: To provide an overview of the principles, safety and efficacy of adoptive cell therapy (ACT) in solid tumors particularly in gynecological cancers. RECENT FINDINGS: Efforts to target solid tumors using tumor-infiltrating lymphocytes and genetically modified T cells have shown promising efficacy in some patients. Two food and drug administration approvals for the treatment of leukemia are the first gene therapies available for cancer treatment in the United States...
December 7, 2017: Current Opinion in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29226251/tissue-based-biomarkers-in-prostate-cancer
#8
Timothy N Clinton, Aditya Bagrodia, Yair Lotan, Vitaly Margulis, Ganesh V Raj, Solomon L Woldu
Introduction: Prostate cancer is a heterogeneous disease. Existing risk stratification tools based on standard clinlicopathologic variables (prostate specific antigen [PSA], Gleason score, and tumor stage) provide a modest degree of predictive ability. Advances in high-throughput sequencing has led to the development of several novel tissue-based biomarkers that can improve prognostication in prostate cancer management. Areas Covered: The authors review commercially-available, tissue-based biomarker assays that improve upon existing risk-stratification tools in several areas of prostate cancer management, including the appropriateness of active surveillance and aiding in decision making regarding the use of adjuvant therapy...
2017: Expert Review of Precision Medicine and Drug Development
https://www.readbyqxmd.com/read/29225271/clinical-relapse-of-anti-ampa-receptor-encephalitis-associated-with-recurrence-of-thymoma
#9
Tsubasa Omi, Makoto Kinoshita, Akira Nishikawa, Takahito Tomioka, Kenichi Ohmori, Kei Fukada, Hidenori Matsunaga
We report a rare case of anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis presenting clinical relapse in association with recurrence of thymoma. Anti-AMPAR encephalitis is an autoimmune-mediated neurological disease, frequently accompanied by the presence of neoplasms, thus comprising the spectrum of paraneoplastic syndrome. A patient had been in remission for 34 months showed clinical relapse 3 months after the detection of recurrent thymoma. Clinical relapse of anti-AMPAR encephalitis after the recurrence of an initially detected neoplasm has not been previously reported...
December 8, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29224003/human-leukocyte-antigen-g-inhibits-the-anti-tumor-effect-of-natural-killer-cells-via-immunoglobulin-like-transcript-2-in-gastric-cancer
#10
Rui Wan, Zi-Wei Wang, Hui Li, Xu-Dong Peng, Guang-Yi Liu, Jun-Ming Ou, An-Qi Cheng
BACKGROUND/AIMS: Human leukocyte antigen-G (HLA-G) plays an important role in inhibiting natural killer (NK) cell function and promoting immune escape. However, the specific mechanism of HLA-G on NK in gastric cancer (GC) remains not well understood. This study investigated the expression of HLA-G in GC and the role of HLA-G-effected NK cells in GC progression. METHODS: HLA-G expression in GC tissues obtained from 49 patients with GC was analyzed by immunohistochemistry and western blot...
December 7, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29222323/graft-versus-tumor-effects-and-why-people-relapse
#11
REVIEW
J H Frederik Falkenburg, Inge Jedema
Graft-versus-tumor (GVT) reactivity mediated by donor T cells in the context of allogeneic stem cell transplantation (alloSCT) is one of the most potent forms of cellular immunotherapy. The antitumor effect against hematologic malignancies is mediated by a polyclonal T-cell response targeting polymorphic antigens expressed on hematopoietic tissues of the recipient, leaving donor hematopoiesis in the patient after transplantation unharmed. Fortunately, hematopoietic tissues (including malignant hematopoietic cell populations) are relatively susceptible to T-cell recognition...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222313/developing-t-cell-therapies-for-lymphoma-without-receptor-engineering
#12
REVIEW
Melanie Grant, Catherine M Bollard
T-cell therapy has emerged from the bench for the treatment of patients with lymphoma. Responses to T-cell therapeutics are regulated by multiple factors, including the patient's immune system status and disease stage. Outside of engineering of chimeric antigen receptors and artificial T-cell receptors, T-cell therapy can be mediated by ex vivo expansion of antigen-specific T cells targeting viral and/or nonviral tumor-associated antigens. These approaches are contributing to enhanced clinical responses and overall survival...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29220404/pymt-maclow-a-novel-inducible-murine-model-for-determining-the-role-of-cd68-positive-cells-in-breast-tumor-development
#13
Robin M H Rumney, Seth B Coffelt, Terence A Neale, Sandeep Dhayade, Gillian M Tozer, Gaynor Miller
CD68+ tumor-associated macrophages (TAMs) are pro-tumorigenic, pro-angiogenic and are associated with decreased survival rates in patients with cancer, including breast cancer. Non-specific models of macrophage ablation reduce the number of TAMs and limit the development of mammary tumors. However, the lack of specificity and side effects associated with these models compromise their reliability. We hypothesized that specific and controlled macrophage depletion would provide precise data on the effects of reducing TAM numbers on tumor development...
2017: PloS One
https://www.readbyqxmd.com/read/29220291/emerging-targeted-and-immune-based-therapies-in-sarcoma
#14
Seth M Pollack, Matthew Ingham, Matthew B Spraker, Gary K Schwartz
Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29219059/inhibition-of-intercellular-communication-between-prostate-cancer-cells-by-a-specific-anti-steap-1-single-chain-antibody
#15
Seyed-Alireza Esmaeili, Foroogh Nejatollahi, Amirhossein Sahebkar
BACKGROUND: Six-Transmembrane epithelial antigen of the prostate-1 (STEAP-1) is present at the intercellular junctions of the secretory epithelium of prostate and is overexpressed in all steps of prostate cancer. STEAP-1 acts as a transporter protein or a putative channel between cancer cells while it has limited expression in normal human tissues. This protein has been suggested as an attractive target for prostate cancer immunotherapy. OBJECTIVE: This study aimed at the development of a specific single chain fragment variable (scFv) antibody against STEAP-1 epitope and testing the inhibitory effect of the selected scFv antibody in blocking gap junctions between tumor cells...
December 7, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29217585/patient-hla-class-i-genotype-influences-cancer-response-to-checkpoint-blockade-immunotherapy
#16
Diego Chowell, Luc G T Morris, Claud M Grigg, Jeffrey K Weber, Robert M Samstein, Vladimir Makarov, Fengshen Kuo, Sviatoslav M Kendall, David Requena, Nadeem Riaz, Benjamin Greenbaum, James Carroll, Edward Garon, David M Hyman, Ahmet Zehir, David Solit, Michael Berger, Ruhong Zhou, Naiyer A Rizvi, Timothy A Chan
CD8+ T cell-dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti-PD-1 or anti-CTLA-4 is currently unknown. We determined the HLA-I genotype of 1,535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci (A, B, and C) improved overall survival after ICB compared to patients who were homozygous for at least one HLA locus...
December 7, 2017: Science
https://www.readbyqxmd.com/read/29217527/merkel-cell-carcinoma-in-the-age-of-immunotherapy-facts-and%C3%A2-hopes
#17
Aric Colunga, Thomas Pulliam, Paul Nghiem
Merkel cell carcinoma (MCC) is a rare (~2,000 US cases/year) but aggressive neuroendocrine tumor of the skin. For advanced MCC, cytotoxic chemotherapy only infrequently (<10% of cases) offers durable clinical responses (>1 year) suggesting a great need for improved therapeutic options. In 2008, the Merkel cell polyomavirus (MCPyV) was discovered and is clonally integrated in ~80% of MCC tumors. The remaining 20% of MCC tumors have large numbers of UV-associated mutations. Importantly, both the UV-induced-neoantigens in virus-negative tumors and the MCPyV T antigen oncogenes that are required for virus-positive tumor growth are immunogenic...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29216863/ccl5-ccr5-interactions-modulate-metabolic-events-during-tumor-onset-to-promote-tumorigenesis
#18
Darrin Gao, Lisa H Cazares, Eleanor N Fish
BACKGROUND: In earlier studies we have shown that CCL5 activation of CCR5 induces the proliferation and survival of breast cancer cells in a mechanistic target of rapamycin (mTOR)-dependent manner and that this is in part due to CCR5-mediated increases in glycolytic metabolism. METHODS: Using the MDA-MB-231 triple negative human breast cancer cell line and mouse mammary tumor virus - polyomavirus middle T-antigen (MMTV-PyMT) mouse primary breast cancer cells, we conducted in vivo tumor transplant experiments to examine the effects of CCL5-CCR5 interactions in the context of regulating tumor metabolism...
December 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29216561/design-synthesis-and-evaluation-of-an-anthraquinone-derivative-conjugated-to-myelin-basic-protein-immunodominant-mbp85-99-epitope-towards-selective-immunosuppression
#19
Anthi Tapeinou, Efstathia Giannopoulou, Carmen Simal, Bjarke E Hansen, Haralabos Kalofonos, Vasso Apostolopoulos, Alexios Vlamis-Gardikas, Theodore Tselios
Anthraquinone type compounds, especially di-substituted amino alkylamino anthraquinones have been widely studied as immunosuppressants. The anthraquinone ring is part of mitoxandrone that has been used for the treatment of multiple sclerosis (MS) and several types of tumors. A desired approach for the treatment of MS would be the immunosuppression and elimination of specific T cells that are responsible for the induction of the disease. Herein, the development of a peptide compound bearing an anthraquinone derivative with the potential to specifically destroy the encephalitogenic T cells responsible for the onset of MS is described...
November 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29212947/requirement-of-treg-intrinsic-ctla4-pkc%C3%AE-signaling-pathway-for-suppressing-tumor-immunity
#20
Christophe Pedros, Ann J Canonigo-Balancio, Kok-Fai Kong, Amnon Altman
The ability of Tregs to control the development of immune responses is essential for maintaining immune system homeostasis. However, Tregs also inhibit the development of efficient antitumor responses. Here, we explored the characteristics and mechanistic basis of the Treg-intrinsic CTLA4/PKCη signaling pathway that we recently found to be required for contact-dependent Treg-mediated suppression. We show that PKCη is required for the Treg-mediated suppression of tumor immunity in vivo. The presence of PKCη-deficient (Prkch-/-) Tregs in the tumor microenvironment was associated with a significantly increased expression of the costimulatory molecule CD86 on intratumoral CD103+ DCs, enhanced priming of antigen-specific CD8+ T cells, and greater levels of effector cytokines produced by these cells...
December 7, 2017: JCI Insight
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