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Tumor immunotherapy

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https://www.readbyqxmd.com/read/29232467/immunotherapy-in-ovarian-cancer
#1
K Odunsi
Immunological destruction of tumors is a multistep, coordinated process that can be modulated or targeted at several critical points to elicit tumor rejection. These steps in the cancer immunity cycle include: (i) generation of sufficient numbers of effector T cells with high avidity recognition of tumor antigens in vivo; (ii) trafficking and infiltration into the tumor; (iii) overcoming inhibitory networks in the tumor microenvironment; (iv) direct recognition of tumor antigens and generation of an effector anti-tumor response; and (v) persistence of the anti-tumor T cells...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29232465/new-treatments-in-ovarian-cancer
#2
E Pujade-Lauraine
In targeting DNA repair pathways of the most genomic instable cancer, poly-(adenosine diphosphate [ADP])-ribose polymerase inhibitors (PARPi) have been demonstrated as the most effective drug since platinum in high grade serous or endometrioid ovarian cancer. Immunotherapy is strongly pushing the door of ovarian cancer and has the ambition to change the fate of this deadly disease when combined with chemotherapy, vascular endothelial growth factor inhibitor or PARPi. The activity of PARPi could also be improved by modulators of the cell cycle, which are required to give time enough for DNA repair...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29230151/integrating-a-19f-mri-tracer-agent-into-the-clinical-scale-manufacturing-of-a-t-cell-immunotherapy
#3
Charles F O'Hanlon, Tamara Fedczyna, Shannon Eaker, William D Shingleton, Brooke M Helfer
Leukocyte immunotherapies have made great progress in the treatment of cancer. Recent reports on the treatment of B-cell malignancies using Chimeric Antigen Receptor and affinity enhanced T-Cell Receptor therapies have demonstrated encouraging clinical results. As investigators begin to explore the treatment of solid tumors with these cells, the hurdle of evaluating T-cell homing to and persistence at the site of disease remain. Significant challenges regarding the GMP manufacture and administration of a therapeutic dose of millions to billions of transduced T-cells remain...
2017: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29230121/leptomeningeal-disease-and-the-evolving-role-of-molecular-targeted-therapy-and-immunotherapy
#4
REVIEW
Katharine Hall Thomas, Robert A Ramirez
Background: Leptomeningeal disease (LMD) is a complication that results from solid tumor metastasis. Prognosis is extremely poor. As therapeutic options for solid tumors improve, the rate of LMD continues to increase. Until recently, treatment has been limited to radiation therapy, intrathecal chemotherapy, and systemic chemotherapy, with an overall survival of 2-3 months. Targeted molecular therapy and immunotherapies are promising new options for increasing overall survival and clinical improvement; however, optimal clinical management remains unknown...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29229829/psma-targeted-polyinosine-polycytosine-vector-induces-prostate-tumor-regression-and-invokes-an-antitumor-immune-response-in-mice
#5
Yael Langut, Alaa Talhami, Samarasimhareddy Mamidi, Alexei Shir, Maya Zigler, Salim Joubran, Anna Sagalov, Efrat Flashner-Abramson, Nufar Edinger, Shoshana Klein, Alexander Levitzki
There is an urgent need for an effective treatment for metastatic prostate cancer (PC). Prostate tumors invariably overexpress prostate surface membrane antigen (PSMA). We designed a nonviral vector, PEI-PEG-DUPA (PPD), comprising polyethylenimine-polyethyleneglycol (PEI-PEG) tethered to the PSMA ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid (DUPA), to treat PC. The purpose of PEI is to bind polyinosinic/polycytosinic acid (polyIC) and allow endosomal release, while DUPA targets PC cells. PolyIC activates multiple pathways that lead to tumor cell death and to the activation of bystander effects that harness the immune system against the tumor, attacking nontargeted neighboring tumor cells and reducing the probability of acquired resistance and disease recurrence...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29229670/kras-and-tumor-immunity-friend-or-foe
#6
Jane Cullis, Shipra Das, Dafna Bar-Sagi
With the recent breakthroughs in immunotherapy as curative treatments in certain tumor types, there has been renewed interest in the relationship between immunity and tumor growth. Although we are gaining a greater understanding of the complex interplay of immune modulating components in the tumor microenvironment, the specific role that tumor cells play in shaping the immune milieu is still not well characterized. In this review, we focus on how mutant Kras tumor cells contribute to tumor immunity, with a specific focus on processes induced directly or indirectly by the oncogene...
December 11, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29229318/low-dose-chemotherapy-combined-with-attenuated-salmonella-decreases-tumor-burden-and-is-less-toxic-than-high-dose-chemotherapy-in-an-autochthonous-murine-model-of-breast-cancer
#7
Daniel Saltzman, Lance Augustin, Arnold Leonard, Michael Mertensotto, Janet Schottel
BACKGROUND: Immunotherapies for cancer treatment have demonstrated substantial promise even though toxicities and development of tumor resistance limit their effectiveness. A combinatorial approach using immunotherapy with other treatment modalities may decrease side effects while maintaining maximal therapeutic effect. We aimed to determine if bacterial immunotherapy in combination with a chemotherapeutic would be efficacious and less toxic than conventional chemotherapy in an established, preclinical, autochthonous tumor model...
December 8, 2017: Surgery
https://www.readbyqxmd.com/read/29228840/investigational-pd-1-inhibitors-in-hl-and-nhl-and-biomarkers-for-predictors-of-response-and-outcome
#8
Andres Chang, Danielle Schlafer, Christopher R Flowers, Pamela B Allen
Inhibitors against the PD-1/PD-L1 pathway are revolutionizing the treatment and management of malignancies. Areas covered: We summarize our current understanding of the function of PD-1, its role in immune evasion, the clinical data available that support the use of PD-1 antagonist in Hodgkin and non-Hodgkin lymphomas, and potential predictors of response. Expert opinion: We anticipate that in the next 10 years, agents that modulate the immune system such as PD-1 antagonists will be increasingly used in favor over traditional cytotoxic chemotherapeutic agents...
December 12, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29228696/mp0250-a-vegf-and-hgf-neutralizing-darpin%C3%A2-molecule-shows-high-anti-tumor-efficacy-in-mouse-xenograft-and-patient-derived-tumor-models
#9
Ulrike Fiedler, Savira Ekawardhani, Andreas Cornelius, Pat Gilboy, Talitha R Bakker, Ignacio Dolado, Michael T Stumpp, Keith M Dawson
Background: The VEGF/VEGFR and the HGF/cMET pathways are key mediators of the interplay of tumor cells and their microenvironment. However, inhibition of VEGF has been shown to produce only limited clinical benefit and inhibition of the activation of cMET by HGF has not translated into clinical benefit in pivotal trials. MP0250, a DARPin® molecule that specifically inhibits both VEGF and HGF has been developed to explore the clinical potential of dual inhibition of these pathways. Results: MP0250 binding to VEGF and HGF inhibited downstream signalling through VEGFR2 and cMET resulting in inhibition of proliferation of VEGF- and HGF-dependent cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227333/illustrative-cases-for-monitoring-by-quantitative-analysis-of-braf-nras-ctdna-mutations-in-liquid-biopsies-of-metastatic-melanoma-patients-who-gained-clinical-benefits-from-anti-pd1-antibody-therapy
#10
Teofila Seremet, Simon Planken, Max Schreuer, Yanina Jansen, Mélanie Delaunoy, Hakim El Housni, Danielle Lienard, Véronique Del Marmol, Pierre Heimann, Bart Neyns
Anti-programmed death 1 (PD-1) monoclonal antibodies improve the survival of metastatic melanoma patients. Predictive or monitoring biomarkers for response to this therapy could improve the clinical management of these patients. To date, no established biomarkers are available for monitoring the response to immunotherapy. Tumor- specific mutations in circulating tumor DNA (ctDNA) such as BRAF and NRAS mutations for melanoma patients have been proposed for monitoring of immunotherapy response. We present seven illustrative cases for the use of ctDNA BRAF and NRAS mutations' monitoring in plasma...
December 8, 2017: Melanoma Research
https://www.readbyqxmd.com/read/29227304/cell-based-immunotherapy-in-gynecologic-malignancies
#11
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/29227119/-molecular-pathology-of-lung-cancer-in-routine-diagnostic-practice-2017-update
#12
Radoslav Matěj, Zdeněk Rohan, Kristýna Němejcová, Pavel Dundr
The group of non-small cell lung carcinomas includes tumors that are variable at the clinical, histopathological and molecular levels. Advances in the understanding of molecular pathology of lung adenocarcinomas in particular led to changes in their histopathological classification and treatment. Patients diagnosed with lung adenocarcinoma harboring specific mutations benefit from the administration of specific targeted therapy. Analysis of EGFR gene mutations and ALK rearrangement in lung adenocarcinomas are already routinely performed and are closely related to the indication for the administration of tyrosinkinase inhibitors...
2017: Ceskoslovenská Patologie
https://www.readbyqxmd.com/read/29226734/emerging-first-line-treatment-options-for-bladder-cancer-a-review-of-phase-ii-and-iii-therapies-in-the-pipeline
#13
Omer Jamy, Guru Sonpavde
The treatment of urothelial carcinoma (UC) had remained unchanged for several years until the recent FDA approval of immune checkpoint inhibitors (CPIs) in the salvage setting. Novel dual CPI-CPI and CPI-chemotherapy combinations are now being investigated aggressively as first line therapy for metastatic disease. Areas Covered: We discuss the recent insights into the tumor biology of UC, which may impact the prognosis as well as assist in developing precision medicine. This is followed by an overview of existing treatment including conventional chemotherapy as well as the trials that led to the recent approval of PD-1 and PD-L1 inhibitors...
December 10, 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/29226090/inhibition-of-il-18-mediated-myeloid-derived-suppressor-cell-accumulation-enhances-anti-pd1-efficacy-against-osteosarcoma-cancer
#14
Ying Guan, Rui Zhang, Zhibin Peng, Daming Dong, Guojun Wei, Yansong Wang
Myeloid derived suppressor cells (MDSC) are very important in tumor immune evasion and they dramatically increased in peripheral blood of patients with osteosarcoma cancer. The association between MDSC and various cytokines has been studied in the peripheral blood. However, little is known about the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and interleukin 18 (IL-18) level in osteosarcoma tumor model and its effect on the immunotherapy. MDSC were isolated from the blood and parenchyma and analyzed in the osteosarcoma tumor model...
November 2017: Journal of Bone Oncology
https://www.readbyqxmd.com/read/29225605/the-state-of-cellular-adoptive-immunotherapy-for-neuroblastoma-and-other-pediatric-solid-tumors
#15
Thanh-Phuong Le, To-Ha Thai
Research on adult cancer immunotherapy is proceeding at a rapid pace resulting in an impressive success rate exemplified by a few high profile cases. However, this momentum is not readily extended to pediatric immunotherapy, and it is not for lack of trying. Though reasons for the slower advance are not apparent, some issues can be raised. Pediatric cancer patients represent a distinct demographic group whose immune system is inherently different from that of mature adults. Treating pediatric patients with immunotherapy designed for adults may not yield objective clinical responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29225184/control-of-polarization-and-tumoricidal-activity-of-macrophages-by-multicellular-spheroid-formation
#16
Yutaro Tanaka, Makiya Nishikawa, Yuya Mizukami, Kosuke Kusamori, Yuka Ogino, Shunsuke Nishimura, Kazunori Shimizu, Satoshi Konishi, Yuki Takahashi, Yoshinobu Takakura
Immune cell-based therapy is a promising approach for cancer immunotherapy. Macrophages can be used for this purpose if their tumoricidal activity and viability are properly controlled. In the present study, we aimed to enhance these properties of macrophages by constructing uniformly sized multicellular spheroids. Mouse macrophage-like J774.1 cells were selected as model macrophages, and poly(N-isopropylacrylamide)-coated polydimethylsiloxane-based microwell plates with an approximate diameter of 750μm were used to prepare J774...
December 7, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29225166/apatinib-inhibits-migration-and-invasion-as-well-as-pd-l1-expression-in-osteosarcoma-by-targeting-stat3
#17
Bingxin Zheng, Tingting Ren, Yi Huang, Wei Guo
The cure rate of osteosarcoma has not improved in the past 30 years. The new treatments and drugs is urgently needed, especially for metastatic osteosarcoma. Anti-angiogenesis therapy and immunotherapy has got promising anti-tumor effects in various tumors. It is hypothesised that combining checkpoint inhibitor immunotherapies with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments. However, its underlying mechanism remain largely uninvestigated. To investigate the clinical significance of vascular endothelial growth factor receptor-2 (VEGFR2) and programmed death ligand-1 (PD-L1) in osteosarcoma, we analyzes their expression levels in 93 osteosarcoma specimens by immunohistochemistry...
December 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29224713/veterinary-oncology-immunotherapies
#18
REVIEW
Philip J Bergman
The ideal cancer immunotherapy agent should be able to discriminate between cancer and normal cells, be potent enough to kill small or large numbers of tumor cells, and be able to prevent recurrence of the tumor. Tumor immunology and immunotherapy are among the most exciting and rapidly expanding fields; cancer immunotherapy is now recognized as a pillar of treatment alongside traditional modalities. This article highlights approaches that seem to hold particular promise in human clinical trials and many that have been tested in veterinary medicine...
December 7, 2017: Veterinary Clinics of North America. Small Animal Practice
https://www.readbyqxmd.com/read/29224274/-correlation-analysis-of-pd-l1-expression-and-prognosis-in-triple-negative-breast-cancers
#19
B J Pan, C Xu, G Q Ping, G X Song, W M Zhang, C Wang, Z H Zhang
Objective: To investigate the relationship between PD-L1 expression and the clinicopathologic features and prognosis in triple-negative breast carcinomas (TNBC). Methods: All 142 cases of TNBC were collected from the First Affiliated Hospital of Nanjing Medical University from February 2011 to December 2014, and the surgical excision or biopsy specimens from patients without chemotherapy and radiotherapy were included. Histopathologic analysis of stromal tumor infiltrating lymphocyte (sTIL) was performed on HE sections, and PD-L1 immunohistochemical staining was done with MaxVision...
December 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29224228/newcastle-disease-virus-ndv-co-expressing-il7-and-il15-modified-tumor-cells-as-a-vaccine-for-cancer-immunotherapy
#20
Xiaojing Xu, Qing Sun, Yu Mei, Yonghao Liu, Lixiang Zhao
IL15 and IL7 are two cytokines essential for T cell development and homeostasis. In order to improve the antitumor activity by Newcastle Disease Virus (NDV)-modified tumor vaccine, we generated a recombinant NDV co-expressing IL15 and IL7 (LX/IL(15+7)) by incorporation of a 2A self-processing peptide into IL15 and IL7 using reverse genetics. B16 cells infected with LX/IL(15+7) expressed both IL15 and IL7 stably. The cytotoxicity assay showed that murine melanoma cells modified with LX/IL(15+7) could significantly enhance the antitumor immune response in vitro...
December 10, 2017: Cancer Science
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