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Carl H June

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https://www.readbyqxmd.com/read/28255718/studying-immunoreceptor-signaling-in-human-t-cells-using-electroporation-of-in-vitro-transcribed-mrna
#1
Omkar Kawalekar, Carl H June, Michael C Milone
The recognition bestowed upon T lymphocytes as key mediators of cellular immunity has been further attested by recent successful clinical studies using genetically modified T cells. With an ever-growing interest in the application of T cells to treat human malignancies, studying the molecular mechanisms of T cell activation, signaling, and function has become imperative. This, therefore, calls for the development of new easy-to-use and accurate models to investigate the biological phenomena that begin at the synaptic levels of T cell and antigen interactions to the ultimate exhaustion and death of the T cell...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28246194/optimized-depletion-of-chimeric-antigen-receptor-t-cells-in-murine-xenograft-models-of-human-acute-myeloid-leukemia
#2
Sarah K Tasian, Saad S Kenderian, Feng Shen, Marco Ruella, Olga Shestova, Miroslaw Kozlowski, Yong Li, April Schrank-Hacker, Jennifer J D Morrissette, Martin Carroll, Carl H June, Stephan A Grupp, Saar Gill
Others and we previously reported potent anti-leukemia efficacy of CD123-redirected chimeric antigen receptor (CAR) T-cells in preclinical human acute myeloid leukemia (AML) models at cost of severe hematologic toxicity. This observation raises concern for potential myeloablation in patients with AML treated with CD123-redirected CAR T-cells and mandates novel approaches for toxicity mitigation. We hypothesized that CAR T-cell depletion with optimal timing after AML eradication would preserve leukemia remission and allow subsequent hematopoietic stem cell transplantation...
February 28, 2017: Blood
https://www.readbyqxmd.com/read/28207696/cancer-killers
#3
Avery D Posey, Carl H June, Bruce L Levine
No abstract text is available yet for this article.
February 14, 2017: Scientific American
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/28187291/the-principles-of-engineering-immune-cells-to-treat-cancer
#5
REVIEW
Wendell A Lim, Carl H June
Chimeric antigen receptor (CAR) T cells have proven that engineered immune cells can serve as a powerful new class of cancer therapeutics. Clinical experience has helped to define the major challenges that must be met to make engineered T cells a reliable, safe, and effective platform that can be deployed against a broad range of tumors. The emergence of synthetic biology approaches for cellular engineering is providing us with a broadly expanded set of tools for programming immune cells. We discuss how these tools could be used to design the next generation of smart T cell precision therapeutics...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28180045/juvenile-nasal-angiofibromas-a-comparison-of-modern-staging-systems-in-an-endoscopic-era
#6
Nicholas R Rowan, Nathan T Zwagerman, Molly E Heft-Neal, Paul A Gardner, Carl H Snyderman
Objectives To compare the clinical utility of four juvenile nasal angiofibroma (JNA) staging systems in a large cohort of patients. Design Retrospective case series. Setting Tertiary referral academic center. Participants Pediatric patients undergoing surgical resection of JNAs between January 2008 and June 2015. Main Outcome Measures Intraoperative blood loss and transfusions, number of staged operations, postoperative residual disease, and recurrent disease. Results In total, 34 patients were identified; all underwent preoperative embolization followed by surgery...
February 2017: Journal of Neurological Surgery. Part B, Skull Base
https://www.readbyqxmd.com/read/28143835/oncolytic-adenoviral-delivery-of-an-egfr-targeting-t-cell-engager-improves-antitumor-efficacy
#7
Carlos A Fajardo, Sonia Guedan, Luis A Rojas, Rafael Moreno, Marcel Arias-Badia, Jana de Sostoa, Carl H June, Ramon Alemany
Antiviral immune responses present a major hurdle to the efficacious use of oncolytic adenoviruses as cancer treatments. Despite the existence of a highly immunosuppressive tumor environment, adenovirus-infected cells can nonetheless be efficiently cleared by infiltrating cytotoxic T lymphocytes (CTL) without compromising tumor burden. In this study, we tested the hypothesis that tumor infiltrating T cells could be more effectively activated and redirected by oncolytic adenoviruses which were armed with bispecific T cell-engager antibodies (BiTE antibodies)...
January 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28031179/pd-1-blockade-modulates-chimeric-antigen-receptor-car-modified-t-cells-refueling-the-car
#8
LETTER
Elise A Chong, J Joseph Melenhorst, Simon F Lacey, David E Ambrose, Vanessa Gonzalez, Bruce L Levine, Carl H June, Stephen J Schuster
No abstract text is available yet for this article.
February 23, 2017: Blood
https://www.readbyqxmd.com/read/28025979/driving-gene-engineered-t-cell-immunotherapy-of-cancer
#9
REVIEW
Laura A Johnson, Carl H June
Chimeric antigen receptor (CAR) gene-engineered T cell therapy holds the potential to make a meaningful difference in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy...
January 2017: Cell Research
https://www.readbyqxmd.com/read/28005491/effect-of-an-otic-milbemycin-oxime-formulation-on-tegastes-acroporanus-infesting-corals
#10
Barrett L Christie, Janis A Raines
The copepod Tegastes acroporanus is a notorious pest of captive corals in the genus Acropora. In recent years, infestations of T. acroporanus have become widespread among public aquaria and coral propagation facilities and have been largely controlled with the extra-label use of milbemycin oxime formulations (Carl 2008). Many of these drug formulations (which were intended for dogs) have been discontinued by their manufacturers in favor of multidrug products, many of which are unsuitable for corals, forcing experimentation with alternatives...
2016: Journal of Aquatic Animal Health
https://www.readbyqxmd.com/read/27959676/drugging-the-undruggable-ras-immunotherapy-to-the-rescue
#11
EDITORIAL
Carl H June
No abstract text is available yet for this article.
December 8, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27887864/optimization-of-cgmp-purification-and-expansion-of-umbilical-cord-blood-derived-t-regulatory-cells-in-support-of-first-in-human-clinical-trials
#12
David H McKenna, Darin Sumstad, Diane M Kadidlo, Bjorn Batdorf, Colin J Lord, Sarah C Merkel, Christine M Koellner, Julie M Curtsinger, Carl H June, James L Riley, Bruce L Levine, Jeffrey S Miller, Claudio G Brunstein, John E Wagner, Bruce R Blazar, Keli L Hippen
BACKGROUND AIMS: Thymic-derived regulatory T cells (tTreg) are critical regulators of the immune system. Adoptive tTreg transfer is a curative therapy for murine models of autoimmunity, graft rejection, and graft-versus-host disease (GVHD). We previously completed a "first-in-human" clinical trial using in vitro expanded umbilical cord blood (UCB)-derived tTreg to prevent GVHD in patients undergoing UCB hematopoietic stem cell transplantation (HSCT). tTreg were safe and demonstrated clinical efficacy, but low yield prevented further dose escalation...
February 2017: Cytotherapy
https://www.readbyqxmd.com/read/27855210/potent-and-broad-inhibition-of-hiv-1-by-a-peptide-from-the-gp41-heptad-repeat-2-domain-conjugated-to-the-cxcr4-amino-terminus
#13
George J Leslie, Jianbin Wang, Max W Richardson, Beth S Haggarty, Kevin L Hua, Jennifer Duong, Anthony J Secreto, Andrea P O Jordon, Josephine Romano, Kritika E Kumar, Joshua J DeClercq, Philip D Gregory, Carl H June, Michael J Root, James L Riley, Michael C Holmes, James A Hoxie
HIV-1 entry can be inhibited by soluble peptides from the gp41 heptad repeat-2 (HR2) domain that interfere with formation of the 6-helix bundle during fusion. Inhibition has also been seen when these peptides are conjugated to anchoring molecules and over-expressed on the cell surface. We hypothesized that potent anti-HIV activity could be achieved if a 34 amino acid peptide from HR2 (C34) were brought to the site of virus-cell interactions by conjugation to the amino termini of HIV-1 coreceptors CCR5 or CXCR4...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27852399/-analysis-of-the-influence-factors-of-school-age-children-s-refractive-status
#14
Z G Chen, M C Chen, J Y Zhang, D Q Cai, Q Wang, S S Lin, J W Chen, H L Zhong
Objective: To analyze the influence of the eye biological parameters, height, and weight on the school-age children's refractive status. Methods: Cross-sectional study. A total of 1 656 children (1 656 eyes), aged from 7 to 14 years, were selected from 8 schools in Wenzhou during June 2012 and June 2013. The height and weight of each child were measured, and the body mass index (BMI) was calculated. The eye biological parameters, including axial length (AL), corneal power (C=1/CR), anterior chamber depth (ACD), and white to white (WTW), were measured by IOLMaster (version 5...
November 11, 2016: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/27815355/multiplex-genome-editing-to-generate-universal-car-t-cells-resistant-to-pd1-inhibition
#15
Jiangtao Ren, Xiaojun Liu, Chongyun Fang, Shuguang Jiang, Carl H June, Yangbing Zhao
PURPOSE: Using gene-disrupted allogeneic T cells as universal effector cells provides an alternative to and potentially improves current chimeric antigen receptor (CAR) T cell therapy against cancers and infectious diseases. EXPERIMENTAL DESIGN: The CRISPR/Cas9 system has recently emerged as a simple and efficient way for multiplex genome engineering. By combining the lentiviral delivery of CAR and CRISPR RNA electroporation to co-introduce RNA encoding the Cas9 and gRNAs targeting endogenous TCR, beta-2 microglobulin (B2M) and PD1 simultaneously, to generate gene-disrupted allogeneic CAR T cells deficient of TCR, HLA class I molecule and PD1...
November 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27745631/evaluating-the-skin-in-patients-undergoing-chimeric-antigen-receptor-modified-t-cell-therapy
#16
Courtney B Rubin, Rosalie Elenitsas, Laura Taylor, Simon F Lacey, Irina Kulikovskaya, Minnal Gupta, Jan J Melenhorst, Alison Loren, Noelle Frey, Carl H June, David Porter, Misha Rosenbach
No abstract text is available yet for this article.
November 2016: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/27668293/a-cure-for-hiv-infection-not-in-my-lifetime-or-just-around-the-corner
#17
Michael M Lederman, Paula M Cannon, Judith S Currier, Carl H June, Hans Peter Kiem, Daniel R Kuritzkes, Sharon R Lewin, David M Margolis, Joseph M McCune, John W Mellors, Timothy W Schacker, Rafick P Sekaly, Pablo Tebas, Bruce D Walker, Daniel C Douek
With the advent and stunning success of combination antiretroviral therapy (ART) to prolong and improve quality of life for persons with HIV infection, HIV research has been afforded the opportunity to pivot towards studies aimed at finding "a cure." The mere idea that cure of HIV might be possible has energized researchers and the community towards achieving this goal. Funding agencies, both governmental and private, have targeted HIV cure as a high priority; many in the field have responded to these initiatives and the cure research agenda is robust...
2016: Pathogens & Immunity
https://www.readbyqxmd.com/read/27632680/cytokine-release-syndrome-after-chimeric-antigen-receptor-t-cell-therapy-for-acute-lymphoblastic-leukemia
#18
Julie C Fitzgerald, Scott L Weiss, Shannon L Maude, David M Barrett, Simon F Lacey, J Joseph Melenhorst, Pamela Shaw, Robert A Berg, Carl H June, David L Porter, Noelle V Frey, Stephan A Grupp, David T Teachey
OBJECTIVE: Initial success with chimeric antigen receptor-modified T cell therapy for relapsed/refractory acute lymphoblastic leukemia is leading to expanded use through multicenter trials. Cytokine release syndrome, the most severe toxicity, presents a novel critical illness syndrome with limited data regarding diagnosis, prognosis, and therapy. We sought to characterize the timing, severity, and intensive care management of cytokine release syndrome after chimeric antigen receptor-modified T cell therapy...
February 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/27584485/peripheral-qct-sector-analysis-reveals-positive-bone-adaptations-following-osteogenic-index-optimized-exercise-2874-board-6-june-3-1-00-pm-3-00-pm
#19
Joseph R Pierce, Kathleen N Beasley, Amanda J Centi, Dennis E Scofield, Charles H Negus, Rachel K Evans, Carl M Maresh, William J Kraemer, Bradley C Nindl
No abstract text is available yet for this article.
May 2016: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/27571406/dual-cd19-and-cd123-targeting-prevents-antigen-loss-relapses-after-cd19-directed-immunotherapies
#20
Marco Ruella, David M Barrett, Saad S Kenderian, Olga Shestova, Ted J Hofmann, Jessica Perazzelli, Michael Klichinsky, Vania Aikawa, Farzana Nazimuddin, Miroslaw Kozlowski, John Scholler, Simon F Lacey, Jan J Melenhorst, Jennifer J D Morrissette, David A Christian, Christopher A Hunter, Michael Kalos, David L Porter, Carl H June, Stephan A Grupp, Saar Gill
Potent CD19-directed immunotherapies, such as chimeric antigen receptor T cells (CART) and blinatumomab, have drastically changed the outcome of patients with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). However, CD19-negative relapses have emerged as a major problem that is observed in approximately 30% of treated patients. Developing approaches to preventing and treating antigen-loss escapes would therefore represent a vertical advance in the field. Here, we found that in primary patient samples, the IL-3 receptor α chain CD123 was highly expressed on leukemia-initiating cells and CD19-negative blasts in bulk B-ALL at baseline and at relapse after CART19 administration...
October 3, 2016: Journal of Clinical Investigation
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