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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/28649003/targeting-egfrviii-for-glioblastoma-multiforme
#2
Ju Yang, Jing Yan, Baorui Liu
Glioblastoma multiforme (GBM) is the most progressive primary brain tumor. Targeting a novel and highly specific tumor antigen is one of the strategies to overcome tumors. EGFR variant III (EGFRvIII) is present in 25%-33% of all patients with GBM and is exclusively expressed on tumor tissue cells. Currently, there are various approaches to target EGFRvIII, including CAR T-cell therapy, therapeutic vaccines, antibodies, and Bi-specific T Cell Engager. In this review, we focus on the preclinical and clinical findings of targeting EGFRvIII for GBM...
June 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28648732/-adoptive-transfer-of-t-lymphocytes
#3
H Vié, B Clémenceau
Within a few years, the success of treatments based on the use of T-cells armed with a chimeric T-receptor for the CD19 molecule (CAR-T CD19) has revolutionized the perception of adoptive transfer approaches. The levels of responses observed in acute leukemias, of the order of 70-90 % are indeed unprecedented. The medical and financial enthusiasm aroused by these results has led to the current situation where more than 300 clinical trials are under way, against some thirty different antigens. This enthusiasm, well justified by the first successes, must however be tempered by the difficulties associated with the use of these cells...
June 22, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/28648487/development-of-novel-avenues-to-overcome-challenges-facing-car-t-cells
#4
REVIEW
Soyeon Kim, Edmund K Moon
There has been dramatic success in treating patients with adoptive transfer of autologous T cells genetically modified to express a chimeric antigen receptor redirecting them to the antigen CD19. Despite this success, the application of chimeric antigen receptor T-cell therapy in solid malignancies has encountered many challenges that need to be overcome if similar success across other cancers is to become a reality. These challenges can be classified into 6 categories: the heterogeneity of tumor cell clones and tumor-associated antigen expression; poor T-cell trafficking into the tumor site; poor T-cell survival and persistence; the presence of suppressive immune cells; the secretion of suppressive soluble factors in the tumor microenvironment; and the upregulation of T-cell intrinsic inhibitory pathways...
June 10, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28641074/development-of-novel-antigen-receptors-for-car-t-cell-therapy-directed-toward-solid-malignancies
#5
REVIEW
David Chen, James Yang
Development of chimeric antigen receptor (CAR) T cells have led to remarkable successes in the treatment of B-cell malignancies with anti-CD19 CAR. Here we discuss the development of novel antigen receptors for use in solid malignancies with respect to target antigens, receptor design, and T cell manipulations.
June 1, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28629762/targeting-the-tumor-and-its-associated-stroma-one-and-one-can-make-three-in-adoptive-t-cell-therapy-of-solid-tumors
#6
Anna Mondino, Gerlanda Vella, Laura Icardi
Adoptive T cell therapy (ACT) has become a promising immunotherapeutic option for cancer patients. The proof for ACT therapeutic efficacy was first obtained with allogenic T cells and then reproduced with T cells isolated from patients' tumor samples (i.e. tumor-infiltrating lymphocytes). It is now clear that specificity of ACT products can be educated by genetically engineering T cells with classical T Cell Receptors (TCR) or chimeric antigen receptors (CAR). To date a poor accessibility of the tumor mass and a hostile microenvironment, influenced by genetic and epigenetic instability, mainly limit ACT therapeutic efficacy in the case of solid tumors...
June 15, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28613086/exploiting-natural-killer-group-2d-receptors-for-car-t-cell-therapy
#7
Benjamin Demoulin, W James Cook, Joana Murad, David J Graber, Marie-Louise Sentman, Caroline Lonez, David E Gilham, Charles L Sentman, Sophie Agaugue
Chimeric antigen receptors (CARs) are genetically engineered proteins that combine an extracellular antigen-specific recognition domain with one or several intracellular T-cell signaling domains. When expressed in T cells, these CARs specifically trigger T-cell activation upon antigen recognition. While the clinical proof of principle of CAR T-cell therapy has been established in hematological cancers, CAR T cells are only at the early stages of being explored to tackle solid cancers. This special report discusses the concept of exploiting natural killer cell receptors as an approach that could broaden the specificity of CAR T cells and potentially enhance the efficacy of this therapy against solid tumors...
June 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/28610774/false-positive-hiv-nucleic-acid-amplification-testing-during-car-t-cell-therapy
#8
Ella J Ariza-Heredia, Bruno P Granwehr, George M Viola, Micah Bhatti, James M Kelley, James Kochenderfer, Chitra Hosing
Advancements in immunotherapy have opened a new era in oncology, to include genetic modification of human T-cells to express a chimeric antigen receptor (CAR) that enables targeted tumor recognition (Kochenderfer et al., 2015; Lee et al., 2015; Maus and Levine 2016; Rosenberg et al., 2008). Herein, we report a false-positive HIV testing in a patient who had undergone CAR T-cell therapy created with a lentiviral vector.
June 3, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28609515/amid-fda-approval-filings-another-car-t-therapy-patient-death
#9
Jennifer Abbasi
No abstract text is available yet for this article.
June 13, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28609257/characteristics-of-participants-enrolled-onto-a-randomized-controlled-trial-of-palliative-care-for-patients-on-phase-i-studies
#10
Betty R Ferrell, Carly L Paterson, Mark T Hughes, Vincent Chung, Marianna Koczywas, Thomas J Smith
INTRODUCTION: Advanced cancer patients participating in phase 1 clinical trials experience considerable symptom burden. Palliative care (PC) may benefit these individuals by providing supportive care during clinical research participation. This study investigates integration of a PC intervention among phase 1 trial participants with advanced cancer. METHODS AND MATERIALS: This study is a multisite randomized clinical trial testing a concurrent PC intervention among phase 1 trial participants...
June 13, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28608730/novel-therapy-for-childhood-acute-lymphoblastic-leukemia
#11
Raoul Santiago, Stéphanie Vairy, Daniel Sinnett, Maja Krajinovic, Henrique Bittencourt
During recent decades, the prognosis of childhood acute lymphoblastic leukemia (ALL) has improved dramatically, nowadays, reaching a cure rate of almost 90%. These results are due to a better management and combination of old therapies, refined risk-group stratification and emergence of minimal residual disease (MRD) combined with treatment's intensification for high-risk subgroups. However, the subgroup of patients with refractory/relapsed ALL still presents a dismal prognosis indicating necessity for innovative therapeutic approaches...
June 13, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28604239/continuing-challenges-and-current-issues-in-acute-lymphoblastic-leukemia
#12
Ankit Kansagra, Saurabh Dahiya, Mark Litzow
Conventional cytotoxic chemotherapy used to treat acute lymphoblastic leukemia (ALL) has resulted into high cure rates for pediatric patients, however outcomes for adult patients remain suboptimal. The 5-year overall survival is only 30-40% in adults and elderly patients with ALL compared to 90% in children. We have seen major advances in our understanding and management of ALL related to identification of new cytogenetic and molecular abnormalities and development of novel targeted agents for the treatment of ALL...
June 11, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28604120/current-and-developing-synthetic-pharmacotherapy-for-treating-relapsed-refractory-multiple-myeloma
#13
Klaus Podar, Martin Pecherstorfer
The introduction of novel agents has significantly improved multiple myeloma (MM) patient outcome during the last two decades. MM received the most drug approvals for any one malignancy during this time period, both in the United States as well as in Europe. Areas covered: Proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies are prototype drug classes, which target both specific MM cell functions, as well as the tumor supportive bone marrow microenvironment, and represent current cornerstones of MM therapy...
June 12, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28596938/genome-edited-t-cell-therapies
#14
REVIEW
Juliette M K M Delhove, Waseem Qasim
PURPOSE OF REVIEW: Alternative approaches to conventional drug-based cancer treatments have seen T cell therapies deployed more widely over the last decade. This is largely due to their ability to target and kill specific cell types based on receptor recognition. Introduction of recombinant T cell receptors (TCRs) using viral vectors and HLA-independent T cell therapies using chimeric antigen receptors (CARs) are discussed. This article reviews the tools used for genome editing, with particular emphasis on the applications of site-specific DNA nuclease mediated editing for T cell therapies...
2017: Current Stem Cell Reports
https://www.readbyqxmd.com/read/28596644/highlights-of-multiple-myeloma-at-the-annual-meeting-of-american-society-of-hematology-2016
#15
REVIEW
Nidhi Tandon, Shaji K Kumar
This review discusses the landmark studies in the field of multiple myeloma (MM) which were presented at American society of hematology annual meeting, 2016. There were contrary results from two large phase III trials (one from US and one from Europe) that evaluated the role of additional interventions like tandem autologous transplant (ASCT) and consolidation after induction therapy followed by ASCT in newly diagnosed MM (NDMM) patients, but there were critical differences between the two studies. Novel agents like carfilzomib and ixazomib proved to be of benefit when used as induction and post ASCT consolidation and maintenance in NDMM...
June 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28588060/sending-car-t-cells-after-multiple-myeloma
#16
(no author information available yet)
Preliminary results from an ongoing phase I clinical trial in China suggest that chimeric antigen receptor T cells engineered to home in on a protein called BCMA may be a potent therapeutic option for multiple myeloma. The therapy was well tolerated and induced complete, durable responses in patients with relapsed/refractory disease.
June 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28578933/extracorporeal-membrane-oxygenation-pulmonary-embolectomy-and-right-ventricular-assist-device-for-massive-pulmonary-embolism
#17
Carly L Lodewyks, Joseph M Bednarczyk, Owen T Mooney, Rakesh C Arora, Rohit K Singal
Consensus regarding the management of massive pulmonary embolism (PE) and persistent shock after thrombolysis is lacking. A 30-year-old man collapsed with massive PE 3 days after an exploratory laparotomy for penetrating trauma, and he remained hypoxic and hypotensive despite thrombolytic therapy. Extracorporeal membrane oxygenation (ECMO) was instituted as a bridge to surgical embolectomy, and placement of a right ventricular assist device (RVAD) was used to facilitate separation from cardiopulmonary bypass...
March 31, 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28561728/adoptive-t-cell-therapy-for-solid-tumors
#18
Oladapo Yeku, Xinghuo Li, Renier J Brentjens
Chimeric antigen receptor (CAR) T-cell therapy is an innovative form of immunotherapy wherein autologous T cells are genetically modified to express chimeric receptors encoding an antigen-specific single-chain variable fragment and various costimulatory molecules. Upon administration, these modified T cells traffic to, and recognize, cancer cells in an HLA-independent manner. CAR T-cell therapy has shown remarkable success in the treatment of CD-19-expressing B-cell acute lymphocytic leukemia. However, clinical gains to the same magnitude have not been reported in solid tumors...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28561703/hematologic-malignancies-plasma-cell-disorders
#19
Madhav V Dhodapkar, Ivan Borrello, Adam D Cohen, Edward A Stadtmauer
Multiple myeloma (MM) is a plasma cell malignancy characterized by the growth of tumor cells in the bone marrow. Properties of the tumor microenvironment provide both potential tumor-promoting and tumor-restricting properties. Targeting underlying immune triggers for evolution of tumors as well as direct attack of malignant plasma cells is an emerging focus of therapy for MM. The monoclonal antibodies daratumumab and elotuzumab, which target the plasma cell surface proteins CD38 and SLAMF7/CS1, respectively, particularly when used in combination with immunomodulatory agents and proteasome inhibitors, have resulted in high response rates and improved survival for patients with relapsed and refractory MM...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28555136/oncolytic-immunotherapy-conceptual-evolution-current-strategies-and-future-perspectives
#20
REVIEW
Zong Sheng Guo, Zuqiang Liu, Stacy Kowalsky, Mathilde Feist, Pawel Kalinski, Binfeng Lu, Walter J Storkus, David L Bartlett
The concept of oncolytic virus (OV)-mediated cancer therapy has been shifted from an operational virotherapy paradigm to an immunotherapy. OVs often induce immunogenic cell death (ICD) of cancer cells, and they may interact directly with immune cells as well to prime antitumor immunity. We and others have developed a number of strategies to further stimulate antitumor immunity and to productively modulate the tumor microenvironment (TME) for potent and sustained antitumor immune cell activity. First, OVs have been engineered or combined with other ICD inducers to promote more effective T cell cross-priming, and in many cases, the breaking of functional immune tolerance...
2017: Frontiers in Immunology
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