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Immunotherapy

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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/28650673/evidence-of-interleukin-21-reduction-in-osteosarcoma-patients-due-to-pd-1-pd-l1-mediated-suppression-of-follicular-helper-t-cell-functionality
#3
Wenwu Gao, Junjie Zhou, Bin Ji
Interleukin 21 (IL-21) is crucial for the development of a robust CD8(+) T cell response and has been shown to promote antitumor immunity. Despite the fact that osteosarcoma presents significant genetic instability with a high immunogenic potential, the antitumor immune response in osteosarcoma is ineffective. We investigated whether this was due to impaired IL-21 responses. We found that the circulating CD4(+) T cells, a major source of IL-21, had reduced capacity to express IL-21 in osteosarcoma patients compared to healthy controls...
June 26, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28650644/combination-of-plant-virus-nanoparticle-based-in-situ-vaccination-with-chemotherapy-potentiates-antitumor-response
#4
Karin L Lee, Abner A Murray, Duc H T Le, Mee Rie Sheen, Sourabh Shukla, Ulrich Commandeur, Steven Fiering, Nicole F Steinmetz
Immunotherapeutics are gaining more traction in the armamentarium used to combat cancer. Specifically, in situ vaccination strategies have gained interest because of their ability to alter the tumor microenvironment to an antitumor state. Herein, we investigate whether flexuous plant virus-based nanoparticles formed by the potato virus X (PVX) can be used as an immunotherapeutic for in situ vaccine monotherapy. We further developed dual chemo-immunotherapeutics by incorporating doxorubicin (DOX) into PVX yielding a dual-functional nanoparticle (PVX-DOX) or by coadministration of the two therapeutic regimes, PVX immunotherapy and DOX chemotherapy (PVX+DOX)...
June 26, 2017: Nano Letters
https://www.readbyqxmd.com/read/28650437/antigen-capturing-nanoparticles-improve-the-abscopal-effect-and-cancer-immunotherapy
#5
Yuanzeng Min, Kyle C Roche, Shaomin Tian, Michael J Eblan, Karen P McKinnon, Joseph M Caster, Shengjie Chai, Laura E Herring, Longzhen Zhang, Tian Zhang, Joseph M DeSimone, Joel E Tepper, Benjamin G Vincent, Jonathan S Serody, Andrew Z Wang
Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties...
June 26, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28650339/ilc2-modulated-t-cell-to-mdsc-balance-is-associated-with-bladder-cancer-recurrence
#6
Mathieu F Chevalier, Sara Trabanelli, Julien Racle, Bérengère Salomé, Valérie Cesson, Dalila Gharbi, Perrine Bohner, Sonia Domingos-Pereira, Florence Dartiguenave, Anne-Sophie Fritschi, Daniel E Speiser, Cyrill A Rentsch, David Gfeller, Patrice Jichlinski, Denise Nardelli-Haefliger, Camilla Jandus, Laurent Derré
Non-muscle-invasive bladder cancer (NMIBC) is a highly recurrent tumor despite intravesical immunotherapy instillation with the bacillus Calmette-Guérin (BCG) vaccine. In a prospective longitudinal study, we took advantage of BCG instillations, which increase local immune infiltration, to characterize immune cell populations in the urine of patients with NMIBC as a surrogate for the bladder tumor microenvironment. We observed an infiltration of neutrophils, T cells, monocytic myeloid-derived suppressor cells (M-MDSCs), and group 2 innate lymphoid cells (ILC2)...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28650043/heme-containing-enzymes-and-inhibitors-for-tryptophan-metabolism
#7
REVIEW
Daojing Yan, Ying-Wu Lin, Xiangshi Tan
Iron-containing enzymes such as heme enzymes play crucial roles in biological systems. Three distinct heme-containing dioxygenase enzymes, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1) and indoleamine 2,3-dioxygenase 2 (IDO2) catalyze the initial and rate-limiting step of l-tryptophan catabolism through the kynurenine pathway in mammals. Overexpression of these enzymes causes depletion of tryptophan and the accumulation of metabolic products, which contributes to tumor immune tolerance and immune dysregulation in a variety of disease pathologies...
June 26, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28649891/new-targeted-therapies-for-relapsed-pediatric-lymphoblastic-leukemia
#8
Joanna Pierro, Laura E Hogan, Teena Bhatla, William L Carroll
The improvement in outcomes for children with acute lymphoblastic leukemia (ALL) is one of the greatest success stories of modern oncology however the prognosis for patients who relapse remains dismal. Recent discoveries by high resolution genomic technologies have characterized the biology of relapsed leukemia, most notably pathways leading to the drug resistant phenotype. These observations open the possibility of targeting such pathways to prevent and/or treat relapse. Likewise, early experiences with new immunotherapeutic approaches have shown great promise...
June 25, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28649648/dramatic-response-of-metaplastic-breast-cancer-to-chemo-immunotherapy
#9
Sylvia Adams
Frequent overexpression of programmed death-ligand 1 has recently been demonstrated in metaplastic breast cancer, which is a rare breast cancer subtype with limited treatment options. This report describes the clinical course of a patient with metastatic metaplastic breast cancer who had a remarkable response to anti-programmed death-1 therapy with pembrolizumab in combination with nab-paclitaxel. Tissue correlates are presented including tumor-infiltrating lymphocytes and high-programmed death-ligand 1 expression in the tumor...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28649604/combined-immunotherapy-with-anti-insulin-resistance-therapy-as-a-novel-therapeutic-strategy-against-neurodegenerative-diseases
#10
Yoshiki Takamatsu, Gilbert Ho, Wakako Koike, Shuei Sugama, Takato Takenouchi, Masaaki Waragai, Jianshe Wei, Kazunari Sekiyama, Makoto Hashimoto
Protein aggregation is a pathological hallmark of and may play a central role in the neurotoxicity in age-associated neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Accordingly, inhibiting aggregation of amyloidogenic proteins, including amyloid β and α-synuclein, has been a main therapeutic target for these disorders. Among various strategies, amyloid β immunotherapy has been extensively investigated in Alzheimer's disease, followed by similar studies of α-synuclein in Parkinson's disease...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28649577/in%C3%A2-vivo-murine-matured-human-cd3-cells-as-a-preclinical-model-for-t-cell-based-immunotherapies
#11
Kevin G Haworth, Christina Ironside, Zachary K Norgaard, Willimark M Obenza, Jennifer E Adair, Hans-Peter Kiem
Adoptive cellular immunotherapy is a promising and powerful method for the treatment of a broad range of malignant and infectious diseases. Although the concept of cellular immunotherapy was originally proposed in the 1990s, it has not seen successful clinical application until recent years. Despite significant progress in creating engineered receptors against both malignant and viral epitopes, no efficient preclinical animal models exist for rapidly testing and directly comparing these engineered receptors...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28649511/why-does-leigh-syndrome-respond-to-immunotherapy
#12
Josef Finsterer, Sinda Zarrouk-Mahjoub
No abstract text is available yet for this article.
June 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28649381/new-cancer-immunotherapy-agents-in-development-a-report-from-an-associated-program-of-the-31-st-annual-meeting-of-the-society-for-immunotherapy-of-cancer-2016
#13
REVIEW
Prasad S Adusumilli, Edward Cha, Mark Cornfeld, Thomas Davis, Adi Diab, Thomas W Dubensky, Elizabeth Evans, Jane L Grogan, Bryan A Irving, Rom S Leidner, Shane A Olwill, Patrick Soon-Shiong, Frederic Triebel, David Tuck, Adrian Bot, Roger D Dansey, Charles G Drake, Gordon J Freeman, Ramy Ibrahim, Salil Patel, Daniel S Chen
This report is a summary of 'New Cancer Immunotherapy Agents in Development' program, which took place in association with the 31st Annual Meeting of the Society for Immunotherapy of Cancer (SITC), on November 9, 2016 in National Harbor, Maryland. Presenters gave brief overviews of emerging clinical and pre-clinical immune-based agents and combinations, before participating in an extended panel discussion with multidisciplinary leaders, including members of the FDA, leading academic institutions and industrial drug developers, to consider topics relevant to the future of cancer immunotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28649247/an-antigen-presenting-and-apoptosis-inducing-polymer-microparticle-prolongs-alloskin-graft-survival-by-selectively-and-markedly-depleting-alloreactive-cd8-t-cells
#14
Wei Wang, Khawar Ali Shahzad, Miaochen Li, Aifeng Zhang, Lei Zhang, Tao Xu, Xin Wan, Chuanlai Shen
Selectively depleting the pathogenic T cells is a fundamental strategy for the treatment of allograft rejection and autoimmune disease since it retains the overall immune function of host. The concept of killer artificial antigen-presenting cells (KaAPCs) has been developed by co-coupling peptide-major histocompatibility complex (pMHC) multimer and anti-Fas monoclonal antibody (mAb) onto the polymeric microparticles (MPs) to induce the apoptosis of antigen-specific T cells. But little information is available about its in vivo therapeutic potential and mechanism...
2017: Frontiers in Immunology
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
#15
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
#16
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/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
#17
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/28648866/cytokines-in-immunogenic-cell-death-applications-for-cancer-immunotherapy
#18
REVIEW
Anne Showalter, Arati Limaye, Jeremiah L Oyer, Robert Igarashi, Christina Kittipatarin, Alicja J Copik, Annette R Khaled
Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28648699/prognostic-factors-and-outcomes-in-metastatic-uveal-melanoma-treated-with-programmed-cell-death-1-or-combined-pd-1-cytotoxic-t-lymphocyte-antigen-4-inhibition
#19
Markus V Heppt, Lucie Heinzerling, Katharina C Kähler, Andrea Forschner, Michael C Kirchberger, Carmen Loquai, Markus Meissner, Friedegund Meier, Patrick Terheyden, Beatrice Schell, Rudolf Herbst, Daniela Göppner, Felix Kiecker, David Rafei-Shamsabadi, Sebastian Haferkamp, Margit A Huber, Jochen Utikal, Mirjana Ziemer, Irmgard Bumeder, Christiane Pfeiffer, Susanne G Schäd, Christoph Schmid-Tannwald, Julia K Tietze, Thomas K Eigentler, Carola Berking
BACKGROUND: Uveal melanoma (UM) is an ocular malignancy with high potential for metastatic spread. In contrast to cutaneous melanoma, immunotherapy has not yet shown convincing efficacy in patients with UM. Combined immune checkpoint blockade with checkpoint programmed cell death-1 (PD-1) and checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibition has not been systematically assessed for UM to date. PATIENTS AND METHODS: Patients with metastatic UM treated with either PD-1 inhibitor monotherapy or combined PD-1 inhibitor and ipilimumab (an anti-CTLA-4 monoclonal antibody) were included from 20 German skin cancer centres...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28648302/nephrotic-syndrome-with-cancer-immunotherapies-a-report-of-2-cases
#20
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
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