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Carl June

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https://www.readbyqxmd.com/read/29158268/car-t-cell-therapies-in-glioblastoma-a-first-look
#1
Denis Migliorini, Pierre-Yves Dietrich, Roger Stupp, Gerald P Linette, Avery D Posey, Carl H June
Glioblastoma is an aggressive malignancy with a poor prognosis. The current standard of care for newly diagnosed glioblastoma patients includes surgery to the extent, temozolomide combined with radiotherapy, and alternating electric fields therapy. After recurrence, there is no standard therapy and survival is less than 9 months. Recurrent glioblastoma offers a unique opportunity to investigate new treatment approaches in a malignancy known for remarkable genetic heterogeneity, immunosuppressive microenvironment and partially permissive anatomical blood brain barrier (BBB)...
November 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29131688/carl-june-speaks-of-his-pioneering-efforts-that-led-to-the-first-food-and-drug-administration-approved-gene-therapy-product
#2
James M Wilson
No abstract text is available yet for this article.
November 13, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/29113627/the-proportion-of-asymptomatic-infections-and-spectrum-of-disease-among-pregnant-women-infected-by-zika-virus-systematic-monitoring-in-french-guiana-2016
#3
Claude Flamand, Camille Fritzell, Séverine Matheus, Maryvonne Dueymes, Gabriel Carles, Anne Favre, Antoine Enfissi, Antoine Adde, Magalie Demar, Mirdad Kazanji, Simon Cauchemez, Dominique Rousset
Zika virus (ZIKV) infection has been associated with complications during pregnancy. Although the presence of symptoms might be a risk factor for complication, the proportion of ZIKV-infected pregnant women with symptoms remains unknown. Following the emergence of ZIKV in French Guiana, all pregnancies in the territory were monitored by RT-PCR and/or detection of ZIKV antibodies. Follow-up data collected during pregnancy monitoring interviews were analysed from 1 February to 1 June 2016. We enrolled 3,050 pregnant women aged 14-48 years and 573 (19%) had laboratory-confirmed ZIKV infection...
November 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/29109077/safety-and-efficacy-of-intratumoral-injections-of-chimeric-antigen-receptor-car-t-cells-in-metastatic-breast-cancer
#4
Julia Tchou, Yangbing Zhao, Bruce L Levine, Paul J Zhang, Megan M Davis, Jan Joseph Melenhorst, Irina Kulikovskaya, Andrea L Brennan, Xiajun Liu, Simon F Lacey, Avery Posey, Austin D Williams, Alycia So, Jose R Conejo-Garcia, Gabriela Plesa, Regina M Young, Shannon McGettigan, Jean Campbell, Robert H Pierce, Jennifer M Matro, Angela M DeMichele, Amy S Clark, Laurence J N Cooper, Lynn M Schuchter, Robert H Vonderheide, Carl H June
Chimeric antigen receptors (CARs) are synthetic molecules that provide new specificities to T cells. Although successful in treatment of hematologic malignancies, CAR T cells are ineffective for solid tumors to date. We found that the cell-surface molecule c-Met was expressed in ~50% of breast tumors, prompting the construction of a CAR T cell specific for c-Met, which halted tumor growth in immune-incompetent mice with tumor xenografts. We then evaluated the safety and feasibility of treating metastatic breast cancer with intratumoral administration of mRNA-transfected c-Met-CAR T cells in a phase 0 clinical trial (NCT01837602)...
November 6, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29074500/cytokine-release-syndrome-associated-with-chimeric-antigen-receptor-t-cell-therapy-clinicopathological-insights
#5
Amrom E Obstfeld, Noelle V Frey, Keith Mansfield, Simon F Lacey, Carl H June, David L Porter, Jan J Melenhorst, Mariusz A Wasik
No abstract text is available yet for this article.
October 26, 2017: Blood
https://www.readbyqxmd.com/read/29051063/defining-optimal-permeant-characteristics-for-ultrasound-mediated-gastrointestinal-delivery
#6
Carl M Schoellhammer, Yiyun Chen, Cody Cleveland, Daniel Minahan, Taylor Bensel, June Y Park, Sarah Saxton, Young-Ah Lucy Lee, Lucas Booth, Robert Langer, Giovanni Traverso
Ultrasound-mediated drug delivery in the gastrointestinal (GI) tract is a bourgeoning area of study. Localized, low-frequency ultrasound has recently been shown to enable significant enhancement in delivery of a broad set of active pharmaceutical ingredients including small molecules, proteins, and nucleic acids without any formulation or encapsulation of the therapeutic. Traditional chemical formulations are typically required to protect, stabilize, and enable the successful delivery of a given therapeutic...
October 16, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29039115/genome-editing-technologies-in-adoptive-t-cell-immunotherapy-for-cancer
#7
REVIEW
Nathan Singh, Junwei Shi, Carl H June, Marco Ruella
PURPOSE OF REVIEW: In this review, we discuss the most recent developments in gene-editing technology and discuss their application to adoptive T cell immunotherapy. RECENT FINDINGS: Engineered T cell therapies targeting cancer antigens have demonstrated significant efficacy in specific patient populations. Most impressively, CD19-directed chimeric antigen receptor T cells (CART19) have led to impressive responses in patients with B-cell leukemia and lymphoma. CTL019, or KYMRIAH™ (tisagenlecleucel), a CD19 CAR T cell product developed by Novartis and the University of Pennsylvania, was recently approved for clinical use by the Food and Drug Administration, representing a landmark in the application of adoptive T cell therapies...
October 16, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29017184/clinical-characteristics-and-outcome-of-60-pediatric-patients-with-malignant-melanoma-registered-with-the-german-pediatric-rare-tumor-registry-step
#8
Sonja Offenmueller, Ulrike Leiter, Benedikt Bernbeck, Claus Garbe, Thomas Eigentler, Arndt Borkhardt, Carl Friedrich Classen, Selim Corbacioglu, Uta Dirksen, Georg Ebetsberger-Dachs, Lucie Heinzerling, Norbert Jorch, Michaela Kuhlen, Jennifer Lawlor, Felix Niggli, Monika Streiter, Dominik T Schneider, Ines Brecht
Background Malignant melanoma (MM) is a common malignancy in adults while it is rare in children. Thus, information on clinical behavior of pediatric MM is incomplete. Patients The German Pediatric Rare Tumor Registry (STEP) presents a prospective analysis of 60 childhood MM cases diagnosed between June 2006 and December 2014. Method Patients' ages ranged between 0 and 17 years at initial diagnosis (median age 9.6 years). Information on patient's and tumor characteristics was obtained by standardized documentation...
November 2017: Klinische Pädiatrie
https://www.readbyqxmd.com/read/28985524/human-genome-editing-in-the-clinic-new-challenges-in-regulatory-benefit-risk-assessment
#9
Mohamed Abou-El-Enein, Toni Cathomen, Zoltán Ivics, Carl H June, Matthias Renner, Christian K Schneider, Gerhard Bauer
As genome editing rapidly progresses toward the realization of its clinical promise, assessing the suitability of current tools and processes used for its benefit-risk assessment is critical. Although current regulations may initially provide an adequate regulatory framework, improvements are recommended to overcome several existing technology-based safety and efficacy issues.
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28983551/association-of-enrollment-in-an-aerodigestive-clinic-with-reduced-hospital-stay-for-children-with-special-health-care-needs
#10
Swathi Appachi, Anne Banas, Lisa Feinberg, Douglas Henry, Diane Kenny, Nathan Kraynack, Amy Rosneck, John Carl, Paul Krakovitz
Importance: Children with special health care needs (CSHCN) have disproportionate health care utilization. Previous studies have demonstrated that a primary medical home improves health care outcomes for this population. Objective: To elucidate if enrollment in a multidisciplinary aerodigestive clinic improves outcomes and reduces health care costs by decreasing admissions and inpatient days. Design, Setting, and Participants: A retrospective medical record review of 113 patients with aerodigestive disorders enrolled in a pediatric multidisciplinary clinic from June 2009 to December 2013 was performed...
November 1, 2017: JAMA Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28970045/absence-of-replication-competent-lentivirus-in-the-clinic-analysis-of-infused-t-cell-products
#11
Kenneth Cornetta, Lisa Duffy, Cameron J Turtle, Michael Jensen, Stephen Forman, Gwendolyn Binder-Scholl, Terry Fry, Anne Chew, David G Maloney, Carl H June
Exposure to replication-competent lentivirus (RCL) is a theoretical safety concern for individuals treated with lentiviral gene therapy. For certain ex vivo gene therapy applications, including cancer immunotherapy trials, RCL detection assays are used to screen the vector product as well as the vector-transduced cells. In this study, we reviewed T cell products screened for RCL using methodology developed in the National Gene Vector Biorepository. All trials utilized third-generation lentiviral vectors produced by transient transfection...
September 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28960172/resting-state-functional-magnetic-resonance-imaging-for-surgical-planning-in-pediatric-patients-a-preliminary-experience
#12
Jarod L Roland, Natalie Griffin, Carl D Hacker, Ananth K Vellimana, S Hassan Akbari, Joshua S Shimony, Matthew D Smyth, Eric C Leuthardt, David D Limbrick
OBJECTIVE Cerebral mapping for surgical planning and operative guidance is a challenging task in neurosurgery. Pediatric patients are often poor candidates for many modern mapping techniques because of inability to cooperate due to their immature age, cognitive deficits, or other factors. Resting-state functional MRI (rs-fMRI) is uniquely suited to benefit pediatric patients because it is inherently noninvasive and does not require task performance or significant cooperation. Recent advances in the field have made mapping cerebral networks possible on an individual basis for use in clinical decision making...
September 29, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28954221/augmentation-of-antitumor-immunity-by-human-and-mouse-car-t-cells-secreting-il-18
#13
Biliang Hu, Jiangtao Ren, Yanping Luo, Brian Keith, Regina M Young, John Scholler, Yangbing Zhao, Carl H June
The effects of transgenically encoded human and mouse IL-18 on T cell proliferation and its application in boosting chimeric antigen receptor (CAR) T cells are presented. Robust enhancement of proliferation of IL-18-secreting human T cells occurred in a xenograft model, and this was dependent on TCR and IL-18R signaling. IL-18 augmented IFN-γ secretion and proliferation of T cells activated by the endogenous TCR. TCR-deficient, human IL-18-expressing CD19 CAR T cells exhibited enhanced proliferation and antitumor activity in the xenograft model...
September 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/28935694/cellular-kinetics-of-ctl019-in-relapsed-refractory-b-cell-acute-lymphoblastic-leukemia-and-chronic-lymphocytic-leukemia
#14
Karen Thudium Mueller, Shannon L Maude, David L Porter, Noelle Frey, Patricia Wood, Xia Han, Edward Waldron, Abhijit Chakraborty, Rakesh Awasthi, Bruce L Levine, J Joseph Melenhorst, Stephan A Grupp, Carl H June, Simon F Lacey
Tisagenlecleucel (CTL019) is an investigational immunotherapy that involves reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor to identify and eliminate CD19-expressing cells. We previously reported that CTL019 achieved impressive clinical efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), including the expansion and persistence of CTL019 cells, which correlates with response to therapy. Here, we performed formal cellular kinetic analyses of CTL019 in a larger cohort of 103 patients treated with CTL019 in 2 different diseases (ALL and CLL)...
September 21, 2017: Blood
https://www.readbyqxmd.com/read/28777789/corrigendum-is-autoimmunity-the-achilles-heel-of-cancer-immunotherapy
#15
Carl H June, Jeremy T Warshauer, Jeffrey A Bluestone
No abstract text is available yet for this article.
August 4, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28768327/the-unified-protocol-for-transdiagnostic-treatment-of-emotional-disorders-compared-with-diagnosis-specific-protocols-for-anxiety-disorders-a-randomized-clinical-trial
#16
RANDOMIZED CONTROLLED TRIAL
David H Barlow, Todd J Farchione, Jacqueline R Bullis, Matthew W Gallagher, Heather Murray-Latin, Shannon Sauer-Zavala, Kate H Bentley, Johanna Thompson-Hollands, Laren R Conklin, James F Boswell, Amantia Ametaj, Jenna R Carl, Hannah T Boettcher, Clair Cassiello-Robbins
Importance: Transdiagnostic interventions have been developed to address barriers to the dissemination of evidence-based psychological treatments, but only a few preliminary studies have compared these approaches with existing evidence-based psychological treatments. Objective: To determine whether the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) is at least as efficacious as single-disorder protocols (SDPs) in the treatment of anxiety disorders...
September 1, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28738791/anthropometric-indices-for-non-pregnant-women-of-childbearing-age-differ-widely-among-four-low-middle-income-populations
#17
K Michael Hambidge, Nancy F Krebs, Ana Garcés, Jamie E Westcott, Lester Figueroa, Shivaprasad S Goudar, Sangappa Dhaded, Omrana Pasha, Sumera Aziz Ali, Antoinette Tshefu, Adrien Lokangaka, Vanessa R Thorsten, Abhik Das, Kristen Stolka, Elizabeth M McClure, Rebecca L Lander, Carl L Bose, Richard J Derman, Robert L Goldenberg, Melissa Bauserman
BACKGROUND: Maternal stature and body mass indices (BMI) of non-pregnant women (NPW) of child bearing age are relevant to maternal and offspring health. The objective was to compare anthropometric indices of NPW in four rural communities in low- to low-middle income countries (LMIC). METHODS: Anthropometry and maternal characteristics/household wealth questionnaires were obtained for NPW enrolled in the Women First Preconception Maternal Nutrition Trial. Body mass index (BMI, kg/m(2)) was calculated...
July 24, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28735493/generating-and-expanding-autologous-chimeric-antigen-receptor-t-cells-from-patients-with-acute-myeloid-leukemia
#18
Saad S Kenderian, Carl H June, Saar Gill
Adoptive transfer of genetically engineered T cells can lead to profound and durable responses in patients with hematologic malignancies, generating enormous enthusiasm among scientists, clinicians, patients, and biotechnology companies. The success of adoptive cellular immunotherapy depends upon the ability to manufacture good quality T cells. We discuss here the methodologies and reagents that are used to generate T cells for the preclinical study of chimeric antigen receptor T cell therapy for acute myeloid leukemia (AML)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28724573/a-single-dose-of-peripherally-infused-egfrviii-directed-car-t-cells-mediates-antigen-loss-and-induces-adaptive-resistance-in-patients-with-recurrent-glioblastoma
#19
Donald M O'Rourke, MacLean P Nasrallah, Arati Desai, Jan J Melenhorst, Keith Mansfield, Jennifer J D Morrissette, Maria Martinez-Lage, Steven Brem, Eileen Maloney, Angela Shen, Randi Isaacs, Suyash Mohan, Gabriela Plesa, Simon F Lacey, Jean-Marc Navenot, Zhaohui Zheng, Bruce L Levine, Hideho Okada, Carl H June, Jennifer L Brogdon, Marcela V Maus
We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28714866/ibrutinib-treatment-improves-t-cell-number-and-function-in-cll-patients
#20
MULTICENTER STUDY
Meixiao Long, Kyle Beckwith, Priscilla Do, Bethany L Mundy, Amber Gordon, Amy M Lehman, Kami J Maddocks, Carolyn Cheney, Jeffrey A Jones, Joseph M Flynn, Leslie A Andritsos, Farrukh Awan, Joseph A Fraietta, Carl H June, Marcela V Maus, Jennifer A Woyach, Michael A Caligiuri, Amy J Johnson, Natarajan Muthusamy, John C Byrd
BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS: Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially...
August 1, 2017: Journal of Clinical Investigation
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