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Immune based cancer therapy

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https://www.readbyqxmd.com/read/29145543/association-of-ipilimumab-with-safety-and-antitumor-activity-in-women-with-metastatic-or-recurrent-human-papillomavirus-related-cervical-carcinoma
#1
Stephanie Lheureux, Marcus O Butler, Blaise Clarke, Mihaela C Cristea, Lainie P Martin, Katia Tonkin, Gini F Fleming, Anna V Tinker, Hal W Hirte, Daliah Tsoref, Helen Mackay, Neesha C Dhani, Prafull Ghatage, Johanne Weberpals, Stephen Welch, Nhu-An Pham, Vinicius Motta, Valentin Sotov, Lisa Wang, Katherine Karakasis, Smitha Udagani, Suzanne Kamel-Reid, Howard Z Streicher, Patricia Shaw, Amit M Oza
Importance: Based on evidence of human papillomavirus (HPV)-induced immune evasion, immunotherapy may be an attractive strategy in cervical cancer. Ipilimumab is a fully humanized monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), which acts to downregulate the T-cell immune response. Objective: To assess the safety and antitumor activity of ipilimumab in recurrent cervical cancer. Design, Setting, and Participants: A multicenter trial was designed for patients with metastatic cervical cancer (squamous cell carcinoma or adenocarcinoma) with measurable disease and progression after at least 1 line of platinum chemotherapy...
November 16, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29145241/the-prognostic-value-of-the-serum-neuron-specific-enolase-and-lactate-dehydrogenase-in-small-cell-lung-cancer-patients-receiving-first-line-platinum-based-chemotherapy
#2
Xiaofan Liu, Weiming Zhang, Wen Yin, Yang Xiao, Changzhi Zhou, Yi Hu, Shuang Geng
The aim of this study was to investigate the associations of serum levels of neuron-specific enolase (NSE), pro-gastrin releasing peptide (ProGRP), and lactate dehydrogenase (LDH) with clinical response and survival in small cell lung cancer (SCLC) patients receiving first-line platinum-based chemotherapy.One hundred thirty-six patients with SCLC were recruited in this study. All the patients received first-line platinum-based chemotherapy. Clinical efficacy was assessed according to Response Evaluation Criteria in Solid Tumors v1...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29144791/is-there-a-role-for-programmed-death-ligand-1-testing-and-immunotherapy-in-colorectal-cancer-with-microsatellite-instability-part-i-colorectal-cancer-microsatellite-instability-testing-and-clinical-implications
#3
Esmeralda Celia Marginean, Barbara Melosky
CONTEXT: - Colorectal cancer (CRC) represents the third most-common cancer in developed countries and is a leading cause of cancer deaths worldwide. Two recognized pathways contribute to CRC development: a more-common chromosomal instability pathway and, in 15% of cases, a deficient mismatch repair or microsatellite instability-high (MSI-H) pathway. The MSI-H CRC can be associated with somatic or germline mutations. Microsatellite status has been recognized as a prognostic and predictive biomarker...
November 16, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29143726/recent-advances-in-vesicular-stomatitis-virus-based-oncolytic-virotherapy-a-5-year-update
#4
Sébastien A Felt, Valery Z Grdzelishvili
Oncolytic virus (OV) therapy is an anti-cancer approach that uses viruses that preferentially infect, replicate in and kill cancer cells. Vesicular stomatitis virus (VSV, a rhabdovirus) is an OV that is currently being tested in the USA in several phase I clinical trials against different malignancies. Several factors make VSV a promising OV: lack of pre-existing human immunity against VSV, a small and easy to manipulate genome, cytoplasmic replication without risk of host cell transformation, independence of cell cycle and rapid growth to high titres in a broad range of cell lines facilitating large-scale virus production...
November 16, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29141863/eight-color-multiplex-immunohistochemistry-for-simultaneous-detection-of-multiple-immune-checkpoint-molecules-within-the-tumor-microenvironment
#5
Mark A J Gorris, Altuna Halilovic, Katrin Rabold, Anne van Duffelen, Iresha N Wickramasinghe, Dagmar Verweij, Inge M N Wortel, Johannes C Textor, I Jolanda M de Vries, Carl G Figdor
Therapies targeting immune checkpoint molecules CTLA-4 and PD-1/PD-L1 have advanced the field of cancer immunotherapy. New mAbs targeting different immune checkpoint molecules, such as TIM3, CD27, and OX40, are being developed and tested in clinical trials. To make educated decisions and design new combination treatment strategies, it is vital to learn more about coexpression of both inhibitory and stimulatory immune checkpoints on individual cells within the tumor microenvironment. Recent advances in multiple immunolabeling and multispectral imaging have enabled simultaneous analysis of more than three markers within a single formalin-fixed paraffin-embedded tissue section, with accurate cell discrimination and spatial information...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29140105/durvalumab-in-non-small-cell-lung-cancer-patients-current-developments
#6
Laura Mezquita, David Planchard
Immune checkpoint inhibitors (ICIs) are a key component of treating advanced cancer patients, principally antibodies against CTLA-4 and PD-1 or PD-L1. Durvalumab (MEDI4736) is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1, which binds to PD-1 and CD80, but not to PD-L2. Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the ≥25% PD-L1+ population. Durvalumab is under evaluation in early, locally advanced and advanced disease as monotherapy and combined with ICIs, targeted therapies, chemotherapy and radiotherapy...
November 15, 2017: Future Oncology
https://www.readbyqxmd.com/read/29137420/anti-angiogenic-and-anti-tumor-effects-of-metronomic-use-of-novel-liposomal-zoledronic-acid-depletes-tumor-associated-macrophages-in-triple-negative-breast-cancer
#7
Xin-Jun Cai, Zeng Wang, Jia-Wei Cao, Jian-Jun Ni, Ying-Ying Xu, Jun Yao, Hong Xu, Fang Liu, Gao-Yi Yang
Zoledronic acid (ZOL) has been used as an adjuvant therapy for breast cancer. It is suggested that ZOL might be associated with inhibition of macrophages, which in turn reduces tumor growth, metastasis and tumor angiogenesis. Moreover, metronomic therapy can inhibit tumor angiogenesis and tumor immune cells. Previously we developed ZOL based cationic liposomes that allowed a higher intratumor delivery of drug compared with free ZOL in vivo. Therefore, in this study, Asn-Gly-Arg (NGR) and PEG2000 were used as ligands to modify the surface of liposomes (NGR-PEG-LP-ZOL) in metronomic therapy to clear the tumor-associated macrophages (TAMs) and inhibit the formation of tumor angiogenesis, achieving the purpose of anti-tumor growth...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135284/atezolizumab-in-urothelial-bladder-carcinoma
#8
Zineb Hamilou, Pernelle Lavaud, Yohann Loriot
Metastatic bladder cancer is an aggressive malignancy with a poor prognosis when presenting with advanced stage. Cisplatin-based therapy has been the mainstay of first-line treatment but therapy in second-line setting has been an unmet medical need for decades. Moreover, many patients are unable to receive cisplatin-based therapy. Recently, immune-checkpoint inhibitors transformed the management and prognosis of many malignancies and will certainly redefine the standard of care for bladder cancer. Atezolizumab, an antiprogrammed cell death ligand-1 antibody, was the first immune-checkpoint inhibitor to be approved by the US FDA in May 2016 for patients with urothelial carcinoma...
November 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/29133939/precision-medicine-for-urothelial-bladder-cancer-update-on-tumour-genomics-and-immunotherapy
#9
REVIEW
Kenneth M Felsenstein, Dan Theodorescu
Effective management of advanced urothelial bladder cancer is challenging. New discoveries that improve our understanding of molecular bladder cancer subtypes have revealed numerous potentially targetable genomic alterations and demonstrated the efficacy of treatments that harness the immune system. These findings have begun to change paradigms of bladder cancer therapy. For example, DNA repair pathway mutations in genes such as ERCC2, FANCC, ATM, RB1, and others can predict responses to neoadjuvant platinum-based chemotherapies and to targeted therapies on the basis of mutation status...
November 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29131143/nonimmune-cells-equipped-with-t-cell-receptor-like-signaling-for-cancer-cell-ablation
#10
Ryosuke Kojima, Leo Scheller, Martin Fussenegger
The ability to engineer custom cell-contact-sensing output devices into human nonimmune cells would be useful for extending the applicability of cell-based cancer therapies and for avoiding risks associated with engineered immune cells. Here we have developed a new class of synthetic T-cell receptor-like signal-transduction device that functions efficiently in human nonimmune cells and triggers release of output molecules specifically upon sensing contact with a target cell. This device employs an interleukin signaling cascade, whose OFF/ON switching is controlled by biophysical segregation of a transmembrane signal-inhibitory protein from the sensor cell-target cell interface...
November 13, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29130882/simultaneous-enumeration-of-cancer-and-immune-cell-types-from-bulk-tumor-gene-expression-data
#11
Julien Racle, Kaat de Jonge, Petra Baumgaertner, Daniel E Speiser, David Gfeller
Immune cells infiltrating tumors can have important impact on tumor progression and response to therapy. We present an efficient algorithm to simultaneously estimate the fraction of cancer and immune cell types from bulk tumor gene expression data. Our method integrates novel gene expression profiles from each major non-malignant cell type found in tumors, renormalization based on cell-type specific mRNA content, and the ability to consider uncharacterized and possibly highly variable cell types. Feasibility is demonstrated by validation with flow cytometry, immunohistochemistry and single-cell RNA-Seq analyses of human melanoma and colorectal tumor specimens...
November 13, 2017: ELife
https://www.readbyqxmd.com/read/29127433/targeting-and-suppression-of-her3-positive-breast-cancer-by-t-lymphocytes-expressing-a-heregulin-chimeric-antigen-receptor
#12
Bai-Le Zuo, Bo Yan, Guo-Xu Zheng, Wen-Jin Xi, Xiao Zhang, An-Gang Yang, Lin-Tao Jia
Chimeric antigen receptor-modulated T lymphocytes (CAR-T) have emerged as a powerful tool for arousing anticancer immunity. Endogenous ligands for tumor antigen may outperform single-chain variable fragments to serve as a component of CARs with high cancer recognition efficacy and minimized immunogenicity. As heterodimerization and signaling partners for human epidermal growth factor receptor 2 (HER2), HER3/HER4 has been implicated in tumorigenic signaling and therapeutic resistance of breast cancer. In this study, we engineered T cells with a CAR consisting of the extracellular domain of heregulin-1β (HRG1β) that is a natural ligand for HER3/HER4, and evaluated the specific cytotoxicity of these CAR-T cells in cultured HER3 positive breast cancer cells and xenograft tumors...
November 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29123947/translational-nanoparticle-engineering-for-cancer-vaccines
#13
REVIEW
Adam J Grippin, Elias J Sayour, Duane A Mitchell
Conventional cancer treatments remain insufficient to treat many therapy-resistant tumors.(1) Cancer vaccines attempt to overcome this resistance by activating the patient's immune system to eliminate tumor cells without the toxicity of systemic chemotherapy and radiation. Nanoparticles (NPs) are promising as customizable, immunostimulatory carriers to protect and deliver antigen. Although many NP vaccines have been investigated in preclinical settings, a few have advanced into clinical application, and still fewer have demonstrated clinical benefit...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123081/resistance-to-cancer-immunotherapy-mediated-by-apoptosis-of-tumor-infiltrating-lymphocytes
#14
Jingjing Zhu, Céline G Powis de Tenbossche, Stefania Cané, Didier Colau, Nicolas van Baren, Christophe Lurquin, Anne-Marie Schmitt-Verhulst, Peter Liljeström, Catherine Uyttenhove, Benoit J Van den Eynde
Despite impressive clinical success, cancer immunotherapy based on immune checkpoint blockade remains ineffective in many patients due to tumoral resistance. Here we use the autochthonous TiRP melanoma model, which recapitulates the tumoral resistance signature observed in human melanomas. TiRP tumors resist immunotherapy based on checkpoint blockade, cancer vaccines or adoptive T-cell therapy. TiRP tumors recruit and activate tumor-specific CD8(+) T cells, but these cells then undergo apoptosis. This does not occur with isogenic transplanted tumors, which are rejected after adoptive T-cell therapy...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29118918/image-guided-dendritic-cell-based-vaccine-immunotherapy-in-murine-carcinoma-models
#15
REVIEW
Bin Wang, Chong Sun, Sijia Wang, Na Shang, Matteo Figini, Quanhong Ma, Shanzhi Gu, Daniele Procissi, Vahid Yaghmai, Guoxin Li, Andrew Larson, Zhuoli Zhang
In recent decades, immunotherapy has undergone extensive developments for oncologic therapy applications. Dendritic cells (DCs) plays a fundamental role in cell-based vaccination immunotherapy against various types of cancer. It involves stimulating innate and adaptive immunity, in particular cytotoxic T-cell mediated antitumor effects, against targeted tumors and has been studied in both preclinical and clinical settings. Nevertheless, clinical outcomes have been unsatisfying. The antitumor response requires sufficient migration of viable DCs from primary administration site to targeted tumors through related lymphatics...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29115428/inhibition-of-p21-activated-kinase-enhances-tumour-immune-response-and-sensitizes-pancreatic-cancer-to-gemcitabine
#16
Kai Wang, Nhi Huynh, Xiao Wang, Graham Baldwin, Mehrdad Nikfarjam, Hong He
Pancreatic ductal adenocarcinoma (PDA) is one of the major types of cancer that exhibit high mortality worldwide because of the late diagnosis and the lack of effective treatment. Immunotherapy appears to be ineffective in PDA treatment due to the existence of a unique immune-suppressive microenvironment in PDA. Gemcitabine-based therapy is still the most commonly used chemotherapy to treat PDA patients with only marginal increased survival rates. This prompted us to continue the search for more effective therapy for PDA treatment...
November 7, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29113194/immune-related-adverse-events-during-anticancer-immunotherapy-pathogenesis-and-management
#17
Stefania Stucci, Raffaele Palmirotta, Anna Passarelli, Erica Silvestris, Antonella Argentiero, Laura Lanotte, Silvana Acquafredda, Annalisa Todisco, Franco Silvestris
Immunotherapy is one of the most recent systemic treatments to emerge for use in oncology, and is based on the blocking of inhibitory immune checkpoints to potentiate the immune response to cancer. The anti-cytotoxic T lymphocyte-associated antigen-4 antibody ipilimumab and anti-programmed cell death protein 1 antibodies, including nivolumab and pembrolizumab, are currently available and widely used, and other immune-inhibiting antibodies are now under intensive investigation. These antibodies have shown efficacy in a growing number of tumor types, following initial observations of their notable effects in melanoma treatment...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29112462/cancer-vaccines-and-immunotherapeutic-approaches-in-hepatobiliary-and-pancreatic-cancers
#18
Inga Hochnadel, Uta Kossatz-Boehlert, Nils Jedicke, Henrike Lenzen, Michael P Manns, Tetyana Yevsa
Hepatobiliary and pancreatic cancers along with other gastrointestinal malignancies remain the leading cause of cancer-related deaths worldwide. Strategies developed in the recent years on immunotherapy and cancer vaccines in the setting of primary liver cancer as well as in pancreatic cancer are the scope of this review. Significance of orthotopic and autochthonous animal models which mimic and/or closely reflect human malignancies allowing for a prompt and trustworthy analysis of new therapeutics is underlined...
November 7, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29109964/immunotherapy-as-a-promising-treatment-for-prostate-cancer-a-systematic-review
#19
REVIEW
Marlena Janiczek, Łukasz Szylberg, Anna Kasperska, Adam Kowalewski, Martyna Parol, Paulina Antosik, Barbara Radecka, Andrzej Marszałek
Prostate cancer treatment is currently based on surgical removal, radiotherapy, and hormone therapy. In recent years, another therapeutic method has emerged-immunological treatment. Immunotherapy modulates and strengthens one's immune responses against cancer. Neoplastic cells naturally escape from the control of the immune system, and the main goal of immune therapy is to bring the control back. Satisfying outcomes after treatment of advanced melanoma and lung cancer suggest a great potential of immunotherapy as an approach for other tumors' treatment, especially in patients primarily introduced to palliative care...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29104575/-hotspots-of-antigen-presentation-revealed-by-human-leukocyte-antigen-ligandomics-for-neoantigen-prioritization
#20
Markus Müller, David Gfeller, George Coukos, Michal Bassani-Sternberg
The remarkable clinical efficacy of the immune checkpoint blockade therapies has motivated researchers to discover immunogenic epitopes and exploit them for personalized vaccines. Human leukocyte antigen (HLA)-binding peptides derived from processing and presentation of mutated proteins are one of the leading targets for T-cell recognition of cancer cells. Currently, most studies attempt to identify neoantigens based on predicted affinity to HLA molecules, but the performance of such prediction algorithms is rather poor for rare HLA class I alleles and for HLA class II...
2017: Frontiers in Immunology
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