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https://www.readbyqxmd.com/read/28813415/cdk4-6-inhibition-triggers-anti-tumour-immunity
#1
Shom Goel, Molly J DeCristo, April C Watt, Haley BrinJones, Jaclyn Sceneay, Ben B Li, Naveed Khan, Jessalyn M Ubellacker, Shaozhen Xie, Otto Metzger-Filho, Jeremy Hoog, Matthew J Ellis, Cynthia X Ma, Susanne Ramm, Ian E Krop, Eric P Winer, Thomas M Roberts, Hye-Jung Kim, Sandra S McAllister, Jean J Zhao
Cyclin-dependent kinases 4 and 6 (CDK4/6) are fundamental drivers of the cell cycle and are required for the initiation and progression of various malignancies. Pharmacological inhibitors of CDK4/6 have shown significant activity against several solid tumours. Their primary mechanism of action is thought to be the inhibition of phosphorylation of the retinoblastoma tumour suppressor, inducing G1 cell cycle arrest in tumour cells. Here we use mouse models of breast carcinoma and other solid tumours to show that selective CDK4/6 inhibitors not only induce tumour cell cycle arrest, but also promote anti-tumour immunity...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28812470/oral-administration-of-ovalbumin-after-sensitization-attenuates-symptoms-in-a-mouse-model-of-food-allergic-enteropathy
#2
Erika Hiraide, Mamiko Morinaga, Hiroki Hidaka, Satoki Yamada, Jun Takeyama, Noriko Kitamura, Osamu Kaminuma, Takachika Hiroi, Weibin Du, Katsuyo Ohashi-Doi, Haruyo Nakajima-Adachi, Satoshi Hachimura
Oral immunotherapy (OIT) is a promising treatment of food allergy. To administer an appropriate oral dose of an allergenic component as OIT to individuals sensitized with a food allergen may prevent inducing food allergic inflammation in them. So we attempted to establish a mouse model to evaluate efficacy for oral administration of food allergen after sensitization. In BALB/c mice sensitized by injecting ovalbumin (OVA) with alum twice, OVA was administered before inducing inflammation by feeding the mice with egg white (EW) diet...
August 16, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28812434/-pemetrexed-sildenafil-via-autophagy-dependent-hdac-down-regulation-enhances-the-immunotherapy-response-of-nsclc-cells
#3
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
Pemetrexed is an approved therapeutic in NSCLC and ovarian cancer. Our studies focused on the ability of [pemetrexed + sildenafil] exposure to alter the immunogenicity of lung and ovarian cancer cells. Treatment of lung and ovarian cancer cells with [pemetrexed + sildenafil] in vitro rapidly reduced the expression of PD-L1, PD-L2 and ornithine decarboxylase (ODC), and increased the expression of Class I MHCA. In a cell-specific fashion, some cells also released the immunogenic nuclear protein HMGB1 into the extracellular environment...
August 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28812098/-radiological-response-assessment-of-modern-immunotherapy-using-irecist
#4
REVIEW
T Persigehl, T D Poeppel, O Sedlaczek
CLINICAL/METHODICAL ISSUE: Modern immunotherapies in oncology show tumor response patterns differing from conventional chemotherapies including initial pseudo-progression. STANDARD RADIOLOGICAL METHODS: Response evaluation criteria in solid tumors (RECIST 1.1) represent the currently most used response criteria for conventional chemotherapy of solid tumors. However, atypical response patterns of immunotherapies are not correctly classified using RECIST 1.1 so that the effectiveness is also incorrectly interpreted...
August 15, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28811980/erap1-overexpression-in-hpv-induced-malignancies-a-possible-novel-immune-evasion-mechanism
#5
Alina Steinbach, Jan Winter, Miriam Reuschenbach, Renata Blatnik, Alexandra Klevenz, Miriam Bertrand, Stephanie Hoppe, Magnus von Knebel Doeberitz, Agnieszka K Grabowska, Angelika B Riemer
Immune evasion of tumors poses a major challenge for immunotherapy. For human papillomavirus (HPV)-induced malignancies, multiple immune evasion mechanisms have been described, including altered expression of antigen processing machinery (APM) components. These changes can directly influence epitope presentation and thus T-cell responses against tumor cells. To date, the APM had not been studied systematically in a large array of HPV(+) tumor samples. Therefore in this study, systematic expression analysis of the APM was performed on the mRNA and protein level in a comprehensive collection of HPV16(+) cell lines...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811976/long-lived-pancreatic-ductal-adenocarcinoma-slice-cultures-enable-precise-study-of-the-immune-microenvironment
#6
Xiuyun Jiang, Y David Seo, Jae Hyuck Chang, Andrew Coveler, Eslam N Nigjeh, Sheng Pan, Florencia Jalikis, Raymond S Yeung, Ian N Crispe, Venu G Pillarisetty
Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease that is rarely cured, despite many recent successes with immunotherapy for other malignancies. As the human disease is heavily infiltrated by effector T cells, we postulated that accurately modeling the PDA immune microenvironment would allow us to study mechanisms of immunosuppression that could be overcome for therapeutic benefit. Using viable precision-cut slices from fresh PDA, we developed an organotypic culture system for this purpose. We confirmed that cultured slices maintain their baseline morphology, surface area, and microenvironment after at least 6 d in culture, and demonstrated slice survival by MTT assay and by immunohistochemistry staining with Ki-67 and cleaved-Caspase-3 antibodies...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811975/chemotherapeutic-agent-mediated-elimination-of-myeloid-derived-suppressor-cells
#7
REVIEW
Zibing Wang, Brian Till, Quanli Gao
Immunotherapy has shown great promise in the fight against cancer, as evidenced by the clinical efficacy of chimeric antigen receptor T cells in hematologic malignancies and checkpoint blockade in certain solid tumors. However, a considerable number of patients fail to respond to these therapies. Induction of myeloid-derived suppressor cells (MDSCs) by growing tumors has been shown to be one important factor limiting the efficacy of cancer immunotherapy. Recently, several chemotherapeutic agents used in conventional cancer chemotherapy have been found to reduce MDSC numbers in tumor tissues as well as in the peripheral lymphoid organs, and combining these agents with immunotherapy improved survival of tumor-bearing hosts...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811971/preclinical-immunopet-ct-imaging-using-zr-89-labeled-anti-pd-l1-monoclonal-antibody-for-assessing-radiation-induced-pd-l1-upregulation-in-head-and-neck-cancer-and-melanoma
#8
Masahiro Kikuchi, David A Clump, Raghvendra M Srivastava, Lingyi Sun, Dexing Zeng, Julio A Diaz-Perez, Carolyn J Anderson, W Barry Edwards, Robert L Ferris
Radiation therapy (RT) can induce upregulation of programmed death ligand 1 (PD-L1) on tumor cells or myeloid cells, which may affect response to PD-1-based immunotherapy. PD-L1 upregulation during RT is a dynamic process that has been difficult to monitor during treatment. The aim of this study was to evaluate the RT-induced PD-L1 upregulation in the tumor and its microenvironment using immunoPET/CT imaging of two syngeneic murine tumor models (HPV+ head and neck squamous cell carcinoma (HNSCC) or B16F10 melanoma)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811970/trial-watch-dendritic-cell-based-anticancer-immunotherapy
#9
REVIEW
Abhishek D Garg, Monica Vara Perez, Marco Schaaf, Patrizia Agostinis, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Dendritic cell (DC)-based vaccines against cancer have been extensively developed over the past two decades. Typically DC-based cancer immunotherapy entails loading patient-derived DCs with an appropriate source of tumor-associated antigens (TAAs) and efficient DC stimulation through a so-called "maturation cocktail" (typically a combination of pro-inflammatory cytokines and Toll-like receptor agonists), followed by DC reintroduction into patients. DC vaccines have been documented to (re)activate tumor-specific T cells in both preclinical and clinical settings...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811969/k27m-mutant-histone-3-as-a-novel-target-for-glioma-immunotherapy
#10
Katharina Ochs, Martina Ott, Theresa Bunse, Felix Sahm, Lukas Bunse, Katrin Deumelandt, Jana K Sonner, Melanie Keil, Andreas von Deimling, Wolfgang Wick, Michael Platten
Mutation-specific vaccines have become increasingly important in glioma immunotherapy; however, shared neoepitopes are rare. For diffuse gliomas, a driver mutation in the gene for isocitrate dehydrogenase type-1 has been shown to produce an immunogenic epitope currently targeted in clinical trials. For highly aggressive midline gliomas, a recurrent point mutation in the histone-3 gene (H3F3A) causes an amino acid change from lysine to methionine at position 27 (K27M). Here, we demonstrate that a peptide vaccine against K27M-mutant histone-3 is capable of inducing effective, mutation-specific, cytotoxic T-cell- and T-helper-1-cell-mediated immune responses in a major histocompatibility complex (MHC)-humanized mouse model...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811966/ceacam1-as-a-multi-purpose-target-for-cancer-immunotherapy
#11
REVIEW
Matthew Dankner, Scott D Gray-Owen, Yu-Hwa Huang, Richard S Blumberg, Nicole Beauchemin
CEACAM1 is an extensively studied cell surface molecule with established functions in multiple cancer types, as well as in various compartments of the immune system. Due to its multi-faceted role as a recently appreciated immune checkpoint inhibitor and tumor marker, CEACAM1 is an attractive target for cancer immunotherapy. Herein, we highlight CEACAM1's function in various immune compartments and cancer types, including in the context of metastatic disease. This review outlines CEACAM1's role as a therapeutic target for cancer treatment in light of these properties...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811965/adjuvant-immunotherapy-with-autologous-dendritic-cells-for-hepatocellular-carcinoma-randomized-phase-ii-study
#12
Jeong-Hoon Lee, Won Young Tak, Yoon Lee, Min-Kyu Heo, Jae-Sung Song, Hak-Yeop Kim, Soo Young Park, Si Hyun Bae, Joon Hyeok Lee, Jeong Heo, Ki-Hwan Kim, Yong-Soo Bae, Yoon Jun Kim
Our previous phase I/IIA study showed that autologous dendritic cells (DCs) pulsed with tumor-associated antigens are well tolerated in patients with hepatocellular carcinoma (HCC). In this randomized, multicenter, open-label, phase II trial, we investigated the efficacy and safety of this DC-based adjuvant immunotherapy with 156 patients, who treated for HCC with no evidence of residual tumor after standard treatment modalities. Patients were randomly assigned to immunotherapy (n = 77; injection of 3 × 10(7) DC cells, six times over 14 weeks) or control (n = 79; no treatment)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811962/an-ror1-bi-specific-t-cell-engager-provides-effective-targeting-and-cytotoxicity-against-a-range-of-solid-tumors
#13
Satyen Harish Gohil, Solange Rosa Paredes-Moscosso, Micaela Harrasser, Marzia Vezzalini, Aldo Scarpa, Emma Morris, Andrew M Davidoff, Claudio Sorio, Amit Chunilal Nathwani, Marco Della Peruta
We have developed a humanized bi-specific T-cell engager (BiTE) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), a cell surface antigen present on a range of malignancies and cancer-initiating cells. Focusing initially on pancreatic cancer, we demonstrated that our ROR1 BiTE results in T cell mediated and antigen-specific cytotoxicity against ROR1-expressing pancreatic cancer cell lines in vitro at exceedingly low concentrations (0.1 ng/mL) and low effector to target ratios. Our BiTE prevented engraftment of pancreatic tumor xenografts in murine models and reduced the size of established subcutaneous tumors by at least 3-fold...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811960/rehmannia-glutinosa-polysaccharide-induces-toll-like-receptor-4-dependent-spleen-dendritic-cell-maturation-and-anti-cancer-immunity
#14
Li Xu, Minseok Kwak, Wei Zhang, Ling Zeng, Peter Chang-Whan Lee, Jun-O Jin
Rehmannia glutinosa polysaccharide (RGP) has shown an activation of immune cells in vitro. However, the immune stimulatory effect of RGP in a mouse in vivo is not well studied. In this study, we examined the effect of RGP on dendritic cell (DC) activation and anticancer immunity in vivo. Treatments of RGP in C56BL/6 mice induced increased levels of co-stimulatory molecule expression and pro-inflammatory cytokine production in spleen DCs dependent on toll-like receptor 4 (TLR4), and those DCs promoted interferon-gamma (IFNγ) production in CD4(+) and CD8(+) T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811959/t-helper-and-t-regulatory-cells-modulation-in-head-and-neck-squamous-cell-carcinoma
#15
REVIEW
Daniele Maggioni, Lorenzo Pignataro, Werner Garavello
Head and neck squamous cell carcinoma (HNSCC) is one of the most diffused cancer types, characterized by a high reoccurrence rate, mainly due to the inability of current therapeutic approaches to completely eradicate cancer cells. HNSCC patients often have defective immune functions, thus allowing cancer immune escape and cancer spreading. Particularly important in driving immune escape during HNSCC progression are T-helper and T-regulatory cells. New insights into their mechanisms of action might support the development of effective and long-lasting immunotherapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811957/mapping-the-human-t-cell-repertoire-to-recurrent-driver-mutations-in-myd88-and-ezh2-in-lymphoma
#16
Julie S Nielsen, Andrew R Chang, Darin A Wick, Colin G Sedgwick, Zusheng Zong, Andrew J Mungall, Spencer D Martin, Natalie N Kinloch, Susann Ott-Langer, Zabrina L Brumme, Steven P Treon, Joseph M Connors, Randy D Gascoyne, John R Webb, Brian R Berry, Ryan D Morin, Nicol Macpherson, Brad H Nelson
Oncogenic "driver" mutations are theoretically attractive targets for the immunotherapy of lymphoid cancers, yet the proportion that can be recognized by T cells remains poorly defined. To address this issue without any confounding effects of the patient's immune system, we assessed T cells from 19 healthy donors for recognition of three common driver mutations in lymphoma: MYD88(L265P), EZH2(Y641F) , and EZH2(Y641N) . Donors collectively expressed the 10 most prevalent HLA class I alleles, including HLA-A*02:01...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811675/biomarkers-matching-mutations-to-immunotherapy-response
#17
Katrina Ray
No abstract text is available yet for this article.
August 16, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28811327/immunotherapy-resistance-genes-identified
#18
(no author information available yet)
A CRISPR-based screen of all 19,050 genes in the genome has revealed around 100 genes that cancer cells must express in order for T cells-and, thus, immunotherapies-to effectively recognize and kill tumors.
August 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28811248/development-of-an-elisa-for-the-diagnosis-of-reactive-ige-antibodies-anti-therapeutic-horse-sera
#19
Salvatore Giovanni De-Simone, Andre Luis Almeida Souza, Aniesse Silva Aguiar, Anibal Raphel Melgarejo, David William Provance-Jr
Hypersensitive diseases that involve IgE reactivity are important concern of public, especially those encompassing the potential pathogenesis from the administration of horse serum-based therapeutics such as antivenoms. A method for the definitive diagnosis of reactive IgE is important for identifying allergic patients to control severe collateral effects during planned and emergency application of immunotherapies when the allergy source cannot be avoided for treatment. To date, no tests have been developed to accompany the wide range of antivenoms produced from horse sera...
August 12, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28810809/optimization-of-human-nk-cell-manufacturing-fully-automated-separation-improved-i-ex-vivo-i-expansion-using-il-21-with-autologous-feeder-cells-and-generation-of-anti-cd123-car-expressing-effector-cells
#20
Stephan Klöß, Olaf Oberschmidt, Michael Morgan, Julia Dahlke, Lubomir Arseniev, Volker Huppert, Markus Granzin, Tanja Gardlowski, Nadine Matthies, Stefanie Soltenborn, Axel Schambach, Ulrike Koehl
BACKGROUND AND AIMS: The administration of ex-vivo expanded Natural killer (NK) cells as potential antitumor effector cells appears to be suitable for effector cell-based immunotherapies in high-risk cancer patients. However, the GMP-conform manufacturing of clinical-grade NK cells at sufficiently high numbers represent a great challenge. Therefore, we improved and optimized previous expansion protocols for those effector cells through the use of newly developed culture medium, IL-21 and autologous feeder cells...
August 16, 2017: Human Gene Therapy
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