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https://www.readbyqxmd.com/read/28215040/who-should-receive-a-transplant-for-acute-lymphoblastic-leukaemia
#1
REVIEW
Rishi Dhawan, David I Marks
Allogeneic haematopoietic cell transplantation continues to be an important curative therapy for acute lymphoblastic leukaemia (ALL). Traditionally accepted indications for allografting adult ALL patients need reevaluation in light of outcomes with paediatric-like intensive regimens. Minimal residual disease status and oncogenetics can be used for restratification of standard risk patients. A greater body of data on haematopoietic cell transplantation (HCT) outcomes from haploidentical and cord blood donor sources has been generated in recent years...
February 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28204981/phase-1b-trial-of-proteasome-inhibitor-carfilzomib-with-irinotecan-in-lung-cancer-and-other-irinotecan-sensitive-malignancies-that-have-progressed-on-prior-therapy-onyx-ist-reference-number-car-ist-553
#2
Susanne M Arnold, Kari Chansky, Markos Leggas, Michael A Thompson, John L Villano, John Hamm, Rachel E Sanborn, Glen J Weiss, Gurkamal Chatta, Maria Q Baggstrom
Introduction Proteasome inhibition is an established therapy for many malignancies. Carfilzomib, a novel proteasome inhibitor, was combined with irinotecan to provide a synergistic approach in relapsed, irinotecan-sensitive cancers. Materials and Methods Patients with relapsed irinotecan-sensitive cancers received carfilzomib (Day 1, 2, 8, 9, 15, and 16) at three dose levels (20/27 mg/m2, 20/36 mg/m2 and 20/45 mg/m2/day) in combination with irinotecan (Days 1, 8 and 15) at 125 mg/m2/day. Key eligibility criteria included measurable disease, a Zubrod PS of 0 or 1, and acceptable organ function...
February 16, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28202953/fully-human-cd19-specific-chimeric-antigen-receptors-for-t-cell-therapy
#3
D Sommermeyer, T Hill, S M Shamah, A I Salter, Y Chen, K M Mohler, S R Riddell
Impressive results have been achieved by adoptively transferring T-cells expressing CD19-specific CARs with binding domains from murine mAbs to treat B-cell malignancies. T-cell mediated immune responses specific for peptides from the murine scFv antigen-binding domain of the CAR can develop in patients and result in premature elimination of CAR-T-cells increasing the risk of tumor relapse. As fully human scFv might reduce immunogenicity, we generated CD19-specific human scFvs with similar binding characteristics as the murine FMC63-derived scFv using human Ab/DNA-libraries...
February 16, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28199983/a-versatile-system-for-rapid-multiplex-genome-edited-car-t-cell-generation
#4
Jiangtao Ren, Xuhua Zhang, Xiaojun Liu, Chongyun Fang, Shuguang Jiang, Carl H June, Yangbing Zhao
The therapeutic potential of CRISPR system has already been demonstrated in many instances and begun to overlap with the rapidly expanding field of cancer immunotherapy, especially on the production of genetically modified T cell receptor or chimeric antigen receptor (CAR) T cells. Efficient genomic disruption of multiple gene loci to generate universal donor cells, as well as potent effector T cells resistant to multiple inhibitory pathways such as PD-1 and CTLA4 is an attractive strategy for cell therapy...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197367/targeting-ewing-sarcoma-with-activated-and-gd2-specific-chimeric-antigen-receptor-engineered-human-nk-cells-induces-upregulation-of-immune-inhibitory-hla-g
#5
Sareetha Kailayangiri, Bianca Altvater, Christian Spurny, Silke Jamitzky, Sonja Schelhaas, Andreas H Jacobs, Constanze Wiek, Katharina Roellecke, Helmut Hanenberg, Wolfgang Hartmann, Heinz Wiendl, Susann Pankratz, Jutta Meltzer, Nicole Farwick, Lea Greune, Maike Fluegge, Claudia Rossig
Activated and in vitro expanded natural killer (NK) cells have substantial cytotoxicity against many tumor cells, but their in vivo efficacy to eliminate solid cancers is limited. Here, we used chimeric antigen receptors (CARs) to enhance the activity of NK cells against Ewing sarcomas (EwS) in a tumor antigen-specific manner. Expression of CARs directed against the ganglioside antigen GD2 in activated NK cells increased their responses to GD2+ allogeneic EwS cells in vitro and overcame resistance of individual cell lines to NK cell lysis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28193774/universal-car-t-cells-successfully-treat-leukemia
#6
(no author information available yet)
Two infants with relapsed, refractory B-cell acute lymphoblastic leukemia went into complete remission after being treated with CD19-targeting CAR T cells derived from an unmatched donor. The study is the first to demonstrate that a universal form of CAR T-cell therapy can be safely utilized.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28186088/current-status-of-immunotherapy-for-gastrointestinal-stromal-tumor
#7
REVIEW
Y Tan, J C Trent, B A Wilky, D A Kerr, A E Rosenberg
Gastrointestinal stromal tumors (GIST) contain tumor-infiltrating immune cells and their presence provides an opportunity and rationale for developing effective forms of immunotherapy. The types of tumor-infiltrating inflammatory cells and relevant immune checkpoint inhibitors are the focus of active investigation. The most numerous tumor-infiltrating inflammatory cells are tumor-associated macrophages (TAMs) and CD3+ T cells. Studies have shown that patients with GISTs that harbor increased numbers of CD3+ T cells have better outcomes...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28178678/the-awakening-of-the-cdk10-cyclin-m-protein-kinase
#8
Vincent J Guen, Carly Gamble, Jacqueline A Lees, Pierre Colas
Cyclin-dependent kinases (CDKs) play important roles in the control of fundamental cellular processes. Some of the most characterized CDKs are considered to be pertinent therapeutic targets for cancers and other diseases, and first clinical successes have recently been obtained with CDK inhibitors. Although discovered in the pre-genomic era, CDK10 attracted little attention until it was identified as a major determinant of resistance to endocrine therapy for breast cancer. In some studies, CDK10 has been shown to promote cell proliferation whereas other studies have revealed a tumor suppressor function...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177911/turn-to-tcrs-when-cars-fail
#9
EDITORIAL
Hans J Stauss
News on: Generation of CD20-specific TCRs for TCR gene therapy of CD20low B-cell malignancies insusceptible to CD20-targetingantibodies by Lorenz Jahn, et al. Oncotarget. 2016; 7(47):77021-77037. doi: 10.18632/oncotarget.12778.
February 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28165252/cocktail-of-superoxide-dismutase-and-fasudil-encapsulated-in-targeted-liposomes-slows-pah-progression-at-a-reduced-dosing-frequency
#10
Nilesh Gupta, Jahidur Rashid, Eva Nozik-Grayck, Ivan F McMurtry, Kurt R Stenmark, Fakhrul Ahsan
Currently, two or more pulmonary vasodilators are used to treat pulmonary arterial hypertension (PAH), but conventional vasodilators alone cannot reverse disease progression. In this study, we tested the hypothesis that a combination therapy comprising a vasodilator plus a therapeutic agent that slows pulmonary arterial remodeling and right heart hypertrophy is an efficacious alternative to current vasodilator-based PAH therapy. Thus, we encapsulated a cocktail of superoxide dismutase (SOD), a superoxide scavenger, and fasudil, a specific rho-kinase inhibitor, into a liposomal formulation equipped with a homing peptide, CAR...
February 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28162024/immunotherapeutic-strategies-for-the-treatment-of-renal-cell-carcinoma-where-will-we-go
#11
Inês Anselmo da Costa, Steffen Rausch, Stephan Kruck, Tilman Todenhöfer, Arnulf Stenzl, Jens Bedke
Historically, renal cell carcinoma (RCC) is considered a chemotherapy-resistant tumor. The cornerstone of systemic therapy included mammalian target of rapamycin (mTOR) inhibitors, endothelial growth factor receptor (VEGFR) and tyrosine kinase inhibitors (TKIs). Currently, a new era is enteres with promising immunotherapeutic treatments, which are becoming commercially available. Areas covered: We provide a comprehensive review using PubMed and ClinicalTrials.gov about the following immunotherapies in RCC: i) vaccine therapy, ii) adoptive T Cell Transfer and CAR T cells, iii) nonspecific immunotherapy-IL-2 (new formulations), iv) Checkpoint inhibitors, v) other checkpoint-molecules...
February 4, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28153859/high-response-to-anti-cd19-car-therapy-in-dlbcl
#12
(no author information available yet)
According to an interim analysis of phase II data from a study of the anti-CD19 chimeric antigen receptor T-cell therapy KTE-C19, 76% of 51 patients with diffuse large B-cell lymphoma responded to the treatment; 47% had a complete response. After 3 months, 33% continued to experience a complete response.
February 2, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28150064/role-of-imaging-in-evaluating-infiltrative-heart-disease
#13
REVIEW
Sanjay Divakaran, Avinainder Singh, Bradley Collins, Tomas Vita, Rodney H Falk, Marcelo F Di Carli, Ron Blankstein
Infiltrative heart disease is caused by the deposition of abnormal substances in the heart and can lead to abnormalities in cardiac function and electrical conduction. Advances in non-invasive cardiovascular imaging have allowed for improved diagnosis of infiltrative heart disease, as well as ways to track disease progression or regression, thus enabling a mechanism to follow response to therapy. In this review, we provide an overview of the role of imaging in the diagnosis and management of cardiac sarcoidosis (CS) and cardiac amyloidosis (CA), as well as outline a proposed algorithm for using non-invasive cardiovascular imaging for evaluating these conditions...
January 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28147896/the-effectiveness-of-lee-silverman-voice-treatment-therapy-issued-interactively-through-an-ipad-device-a-non-inferiority-study
#14
Murray Griffin, John Bentley, Joseph Shanks, Carly Wood
Introduction This study compared the differences in recorded speech variables between people treated with conventional 'in person' Lee Silverman Voice Treatment (LSVT) and those treated remotely via iPad-based 'Facetime'. Method Eight participants were selected for the iPad LSVT, and 21 similarly matched subjects were selected from existing data to form the 'in person' group. Participants in both groups had diagnosed idiopathic Parkinson's disease and moderate hypokinetic dysarthria. Eighteen sessions of prescribed LSVT comprising a pre-treatment assessment, 16 treatment sessions, and a six months' post-treatment assessment were administered for each person...
January 1, 2017: Journal of Telemedicine and Telecare
https://www.readbyqxmd.com/read/28143740/engineering-hiv-resistant-anti-hiv-chimeric-antigen-receptor-t-cells
#15
Malika Hale, Taylor Mesojednik, Guillermo S Romano Ibarra, Jaya Sahni, Alison Bernard, Karen Sommer, Andrew M Scharenberg, David J Rawlings, Thor A Wagner
The treatment or cure of HIV infection by cell and gene therapy has been a goal for decades. Recent advances in both gene editing and chimeric antigen receptor (CAR) technology have created new therapeutic possibilities for a variety of diseases. Broadly neutralizing monoclonal antibodies (bNAbs) with specificity for the HIV envelope glycoprotein provide a promising means of targeting HIV-infected cells. Here we show that primary human T cells engineered to express anti-HIV CARs based on bNAbs (HIVCAR) show specific activation and killing of HIV-infected versus uninfected cells in the absence of HIV replication...
January 28, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28133224/-a-case-of-curatively-resected-locally-advanced-cancer-of-the-pancreatic-body-treated-by-distal-pancreatectomy-with-en-bloc-celiac-axis-resection-after-preoperative-intensive-treatment
#16
Yongkook Kim, Hiromitsu Hoshino, Naruyasu Kakita, Masaru Yamasaki, Yohei Hosoda, Masaya Nishino, Miho Okano, Junji Kawada, Masaki Okuyama, Toshimasa Tsujinaka
A 70-year-old woman with locally advanced pancreatic body cancer invading the celiac axis underwent 4 courses of preoperative chemotherapy consisting of gemcitabine(GEM)plus nab-paclitaxel(nab-PTX)on days 1, 8, and 15 every 4 weeks, followed by radiation therapy(CRT; 50.4Gy delivered in 28 daily fractions). The tumor size was greatly diminished and levels of all tumor markers were decreased. R0resection by distal pancreatectomy with en bloc celiac axis resection(DP-CAR)was performed. The histopathologic findings showed that the effect of CRT was grade 2b(Evans' classification), and the surgical margins were histologically clear...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28133191/-a-case-of-successful-stomach-preserving-pancreaticoduodenectomy-with-celiac-artery-resection-after-neoadjuvant-chemoradiation-therapy-for-pancreatic-cancer-with-hepatic-arterial-variation
#17
Yukie Kyakumoto, Masamichi Mizuma, Tomoya Abe, Tatsuyuki Takadate, Koji Fukase, Hideo Otsuka, Naoaki Sakata, Kei Nakagawa, Takanori Morikawa, Hiroki Hayashi, Takeshi Naitoh, Fuyuhiko Motoi, Atsushi Kanno, Tooru Shimosegawa, Michiaki Unno
Here we report a case of successful stomach-preserving pancreaticoduodenectomy with celiac artery resection for pancreatic cancer with hepatic arterial variation. A 70-year-old woman was referred to our hospital for examination and treatment of pancreatic cancer. A CT scan showed a tumor with suspected portal vein invasion at the body and head of the pancreas, in contact with the common hepatic artery and the splenic artery with 360°involvement. Contact with the celiac artery and left gastric artery was less than1 80°...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28129132/expanding-accessibility-to-cd19-car-t-cells-commercializing-a-boutique-therapy
#18
Premal Lulla, Carlos A Ramos
No abstract text is available yet for this article.
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28129122/phase-1-results-of-zuma-1-a-multicenter-study-of-kte-c19-anti-cd19-car-t-cell-therapy-in-refractory-aggressive-lymphoma
#19
Frederick L Locke, Sattva S Neelapu, Nancy L Bartlett, Tanya Siddiqi, Julio C Chavez, Chitra M Hosing, Armin Ghobadi, Lihua E Budde, Adrian Bot, John M Rossi, Yizhou Jiang, Allen X Xue, Meg Elias, Jeff Aycock, Jeff Wiezorek, William Y Go
Outcomes for patients with refractory diffuse large B cell lymphoma (DLBCL) are poor. In the multicenter ZUMA-1 phase 1 study, we evaluated KTE-C19, an autologous CD3ζ/CD28-based chimeric antigen receptor (CAR) T cell therapy, in patients with refractory DLBCL. Patients received low-dose conditioning chemotherapy with concurrent cyclophosphamide (500 mg/m(2)) and fludarabine (30 mg/m(2)) for 3 days followed by KTE-C19 at a target dose of 2 × 10(6) CAR T cells/kg. The incidence of dose-limiting toxicity (DLT) was the primary endpoint...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28129121/masked-chimeric-antigen-receptor-for-tumor-specific-activation
#20
Xiaolu Han, Paul D Bryson, Yifan Zhao, Gunce E Cinay, Si Li, Yunfei Guo, Natnaree Siriwon, Pin Wang
Adoptive cellular therapy based on chimeric antigen receptor (CAR)-engineered T (CAR-T) cells is a powerful form of cancer immunotherapy. CAR-T cells can be redirected to specifically recognize tumor-associated antigens (TAAs) and induce high levels of antitumor activity. However, they may also display "on-target off-tumor" toxicities, resulting from low-level expression of TAAs in healthy tissues. These adverse effects have raised considerable safety concerns and limited the clinical application of this otherwise promising therapeutic modality...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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