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Carl H June

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https://www.readbyqxmd.com/read/28777789/corrigendum-is-autoimmunity-the-achilles-heel-of-cancer-immunotherapy
#1
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
#2
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/28735493/generating-and-expanding-autologous-chimeric-antigen-receptor-t-cells-from-patients-with-acute-myeloid-leukemia
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28680947/beyond-endemic-burkitt-lymphoma-navigating-challenges-of-differentiating-childhood-lymphoma-diagnoses-amid-limitations-in-pathology-resources-in-lilongwe-malawi
#6
Nader Kim El-Mallawany, Mercy Mutai, Idah Mtete, Satish Gopal, Christopher C Stanley, Peter Wasswa, Mary Mtunda, Mary Chasela, William Kamiyango, Jimmy Villiera, Yuri Fedoriw, Nathan D Montgomery, George N Liomba, Coxcilly Kampani, Robert Krysiak, Katherine D Westmoreland, Maria H Kim, Jeremy S Slone, Michael E Scheurer, Carl E Allen, Parth S Mehta, Peter N Kazembe
Background. Although Burkitt lymphoma (BL) is the most common childhood lymphoma in sub-Saharan Africa, Hodgkin lymphoma (HL) and other non-Hodgkin lymphomas occur. Diagnosing non-jaw mass presentations is challenging with limited pathology resources. Procedure. We retrospectively analyzed 114 pediatric lymphomas in Lilongwe, Malawi, from December 2011 to June 2013 and compared clinical versus pathology-based diagnoses over two time periods. Access to pathology resources became more consistent in 2013 compared with 2011-2012; pathology interpretations were based on morphology only...
2017: Global Pediatric Health
https://www.readbyqxmd.com/read/28640704/immunotherapy-for-brain-tumors
#7
REVIEW
John H Sampson, Marcela V Maus, Carl H June
Glioblastoma (GBM) is the most lethal form of brain tumor and remains a large, unmet medical need. This review focuses on recent advances in the neurosciences that converge with the broader field of immuno-oncology. Recent findings in neuroanatomy provide a basis for new approaches of cellular therapies for tumors that involve the CNS. The ultimate success of immunotherapy in the CNS will require improved imaging technologies and methods for analysis of the tumor microenvironment in patients with GBM. It is likely that combinatorial approaches with targeted immunotherapies will be required to exploit the vulnerabilities of GBM and other brain tumors...
July 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28598276/risk-factors-associated-with-postoperative-cerebrospinal-fluid-leak-after-endoscopic-endonasal-skull-base-surgery
#8
Shannon Fraser, Paul A Gardner, Maria Koutourousiou, Mark Kubik, Juan C Fernandez-Miranda, Carl H Snyderman, Eric W Wang
OBJECTIVE The aim in this paper was to determine risk factors for the development of a postoperative CSF leak after an endoscopic endonasal approach (EEA) for resection of skull base tumors. METHODS A retrospective review of patients who underwent EEA for the resection of intradural pathology between January 1997 and June 2012 was performed. Basic demographic data were collected, along with patient body mass index (BMI), tumor pathology, reconstruction technique, lumbar drainage, and outcomes. RESULTS Of the 615 patients studied, 103 developed a postoperative CSF leak (16...
June 9, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28576927/overcoming-the-immunosuppressive-tumor-microenvironment-of-hodgkin-lymphoma-using-chimeric-antigen-receptor-t-cells
#9
Marco Ruella, Michael Klichinsky, Saad S Kenderian, Olga Shestova, Amy Ziober, Daniel O Kraft, Michael Feldman, Mariusz A Wasik, Carl H June, Saar Gill
Some patients with otherwise treatment-resistant Hodgkin lymphoma (HL) could benefit from chimeric antigen receptor T cell (CART) therapy. However, HL lacks CD19 and contains a highly immunosuppressive tumor microenvironment (TME). We hypothesized that in HL, CART should target both malignant cells and the TME. We demonstrated CD123 on both HL cells and TME, including tumor-associated macrophages (TAM). In vitro, HL cells convert macrophages towards immunosuppressive TAM that inhibit T cell proliferation. In contrast, anti-CD123 CART recognized and killed TAM thus overcoming immunosuppression...
June 2, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28523432/novel-t-cells-with-improved-in-vivo-anti-tumor-activity-generated-by-rna-electroporation
#10
Xiaojun Liu, Shuguang Jiang, Chongyun Fang, Hua Li, Xuhua Zhang, Fuqin Zhang, Carl H June, Yangbing Zhao
The generation of T cells with maximal anti-tumor activities will significantly impact the field of T-cell-based adoptive immunotherapy. In this report, we found that OKT3/IL-2-stimulated T cells were phenotypically more heterogeneous, with enhanced anti-tumor activity in vitro and when locally administered in a solid tumor mouse model. To further improve the OKT3/IL-2-based T cell manufacturing procedure, we developed a novel T cell stimulation and expansion method in which peripheral blood mononuclear cells were electroporated with mRNA encoding a chimeric membrane protein consisting of a single-chain variable fragment against CD3 and the intracellular domains of CD28 and 4-1BB (OKT3-28BB)...
July 2017: Protein & Cell
https://www.readbyqxmd.com/read/28475571/is-autoimmunity-the-achilles-heel-of-cancer-immunotherapy
#11
Carl H June, Jeremy T Warshauer, Jeffrey A Bluestone
The emergence of immuno-oncology as the first broadly successful strategy for metastatic cancer will require clinicians to integrate this new pillar of medicine with chemotherapy, radiation, and targeted small-molecule compounds. Of equal importance is gaining an understanding of the limitations and toxicities of immunotherapy. Immunotherapy was initially perceived to be a relatively less toxic approach to cancer treatment than other available therapies-and surely it is, when compared to those. However, as the use of immunotherapy becomes more common, especially as first- and second-line treatments, immunotoxicity and autoimmunity are emerging as the Achilles' heel of immunotherapy...
May 5, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28384795/child-and-adolescent-health-from-1990-to-2015-findings-from-the-global-burden-of-diseases-injuries-and-risk-factors-2015-study
#12
Nicholas Kassebaum, Hmwe Hmwe Kyu, Leo Zoeckler, Helen Elizabeth Olsen, Katie Thomas, Christine Pinho, Zulfiqar A Bhutta, Lalit Dandona, Alize Ferrari, Tsegaye Tewelde Ghiwot, Simon I Hay, Yohannes Kinfu, Xiaofeng Liang, Alan Lopez, Deborah Carvalho Malta, Ali H Mokdad, Mohsen Naghavi, George C Patton, Joshua Salomon, Benn Sartorius, Roman Topor-Madry, Stein Emil Vollset, Andrea Werdecker, Harvey A Whiteford, Kalkidan Hasen Abate, Kaja Abbas, Solomon Abrha Damtew, Muktar Beshir Ahmed, Nadia Akseer, Rajaa Al-Raddadi, Mulubirhan Assefa Alemayohu, Khalid Altirkawi, Amanuel Alemu Abajobir, Azmeraw T Amare, Carl A T Antonio, Johan Arnlov, Al Artaman, Hamid Asayesh, Euripide Frinel G Arthur Avokpaho, Ashish Awasthi, Beatriz Paulina Ayala Quintanilla, Umar Bacha, Balem Demtsu Betsu, Aleksandra Barac, Till Winfried Bärnighausen, Estifanos Baye, Neeraj Bedi, Isabela M Bensenor, Adugnaw Berhane, Eduardo Bernabe, Oscar Alberto Bernal, Addisu Shunu Beyene, Sibhatu Biadgilign, Boris Bikbov, Cheryl Anne Boyce, Alexandra Brazinova, Gessessew Bugssa Hailu, Austin Carter, Carlos A Castañeda-Orjuela, Ferrán Catalá-López, Fiona J Charlson, Abdulaal A Chitheer, Jee-Young Jasmine Choi, Liliana G Ciobanu, John Crump, Rakhi Dandona, Robert P Dellavalle, Amare Deribew, Gabrielle deVeber, Daniel Dicker, Eric L Ding, Manisha Dubey, Amanuel Yesuf Endries, Holly E Erskine, Emerito Jose Aquino Faraon, Andre Faro, Farshad Farzadfar, Joao C Fernandes, Daniel Obadare Fijabi, Christina Fitzmaurice, Thomas D Fleming, Luisa Sorio Flor, Kyle J Foreman, Richard C Franklin, Maya S Fraser, Joseph J Frostad, Nancy Fullman, Gebremedhin Berhe Gebregergs, Alemseged Aregay Gebru, Johanna M Geleijnse, Katherine B Gibney, Mahari Gidey Yihdego, Ibrahim Abdelmageem Mohamed Ginawi, Melkamu Dedefo Gishu, Tessema Assefa Gizachew, Elizabeth Glaser, Audra L Gold, Ellen Goldberg, Philimon Gona, Atsushi Goto, Harish Chander Gugnani, Guohong Jiang, Rajeev Gupta, Fisaha Haile Tesfay, Graeme J Hankey, Rasmus Havmoeller, Martha Hijar, Masako Horino, H Dean Hosgood, Guoqing Hu, Kathryn H Jacobsen, Mihajlo B Jakovljevic, Sudha P Jayaraman, Vivekanand Jha, Tariku Jibat, Catherine O Johnson, Jost Jonas, Amir Kasaeian, Norito Kawakami, Peter N Keiyoro, Ibrahim Khalil, Young-Ho Khang, Jagdish Khubchandani, Aliasghar A Ahmad Kiadaliri, Christian Kieling, Daniel Kim, Niranjan Kissoon, Luke D Knibbs, Ai Koyanagi, Kristopher J Krohn, Barthelemy Kuate Defo, Burcu Kucuk Bicer, Rachel Kulikoff, G Anil Kumar, Dharmesh Kumar Lal, Hilton Y Lam, Heidi J Larson, Anders Larsson, Dennis Odai Laryea, Janni Leung, Stephen S Lim, Loon-Tzian Lo, Warren D Lo, Katharine J Looker, Paulo A Lotufo, Hassan Magdy Abd El Razek, Reza Malekzadeh, Desalegn Markos Shifti, Mohsen Mazidi, Peter A Meaney, Kidanu Gebremariam Meles, Peter Memiah, Walter Mendoza, Mubarek Abera Mengistie, Gebremichael Welday Mengistu, George A Mensah, Ted R Miller, Charles Mock, Alireza Mohammadi, Shafiu Mohammed, Lorenzo Monasta, Ulrich Mueller, Chie Nagata, Aliya Naheed, Grant Nguyen, Quyen Le Nguyen, Elaine Nsoesie, In-Hwan Oh, Anselm Okoro, Jacob Olusegun Olusanya, Bolajoko O Olusanya, Alberto Ortiz, Deepak Paudel, David M Pereira, Norberto Perico, Max Petzold, Michael Robert Phillips, Guilherme V Polanczyk, Farshad Pourmalek, Mostafa Qorbani, Anwar Rafay, Vafa Rahimi-Movaghar, Mahfuzar Rahman, Rajesh Kumar Rai, Usha Ram, Zane Rankin, Giuseppe Remuzzi, Andre M N Renzaho, Hirbo Shore Roba, David Rojas-Rueda, Luca Ronfani, Rajesh Sagar, Juan Ramon Sanabria, Muktar Sano Kedir Mohammed, Itamar S Santos, Maheswar Satpathy, Monika Sawhney, Ben Schöttker, David C Schwebel, James G Scott, Sadaf G Sepanlou, Amira Shaheen, Masood Ali Shaikh, June She, Rahman Shiri, Ivy Shiue, Inga Dora Sigfusdottir, Jasvinder Singh, Naris Silpakit, Alison Smith, Chandrashekhar Sreeramareddy, Jeffrey D Stanaway, Dan J Stein, Caitlyn Steiner, Muawiyyah Babale Sufiyan, Soumya Swaminathan, Rafael Tabarés-Seisdedos, Karen M Tabb, Fentaw Tadese, Mohammad Tavakkoli, Bineyam Taye, Stephanie Teeple, Teketo Kassaw Tegegne, Girma Temam Shifa, Abdullah Sulieman Terkawi, Bernadette Thomas, Alan J Thomson, Ruoyan Tobe-Gai, Marcello Tonelli, Bach Xuan Tran, Christopher Troeger, Kingsley N Ukwaja, Olalekan Uthman, Tommi Vasankari, Narayanaswamy Venketasubramanian, Vasiliy Victorovich Vlassov, Elisabete Weiderpass, Robert Weintraub, Solomon Weldemariam Gebrehiwot, Ronny Westerman, Hywel C Williams, Charles D A Wolfe, Rachel Woodbrook, Yuichiro Yano, Naohiro Yonemoto, Seok-Jun Yoon, Mustafa Z Younis, Chuanhua Yu, Maysaa El Sayed Zaki, Elias Asfaw Zegeye, Liesl Joanna Zuhlke, Christopher J L Murray, Theo Vos
Importance: Comprehensive and timely monitoring of disease burden in all age groups, including children and adolescents, is essential for improving population health. Objective: To quantify and describe levels and trends of mortality and nonfatal health outcomes among children and adolescents from 1990 to 2015 to provide a framework for policy discussion. Evidence Review: Cause-specific mortality and nonfatal health outcomes were analyzed for 195 countries and territories by age group, sex, and year from 1990 to 2015 using standardized approaches for data processing and statistical modeling, with subsequent analysis of the findings to describe levels and trends across geography and time among children and adolescents 19 years or younger...
June 1, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/28344808/safety-tumor-trafficking-and-immunogenicity-of-chimeric-antigen-receptor-car-t-cells-specific-for-tag-72-in-colorectal-cancer
#13
Kristen M Hege, Emily K Bergsland, George A Fisher, John J Nemunaitis, Robert S Warren, James G McArthur, Andy A Lin, Jeffrey Schlom, Carl H June, Stephen A Sherwin
BACKGROUND: T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s. METHODS: Patients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28255718/studying-immunoreceptor-signaling-in-human-t-cells-using-electroporation-of-in-vitro-transcribed-mrna
#14
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
#15
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
We and others previously reported potent antileukemia efficacy of CD123-redirected chimeric antigen receptor (CAR) T cells in preclinical human acute myeloid leukemia (AML) models at the 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...
April 27, 2017: Blood
https://www.readbyqxmd.com/read/28207696/cancer-killers
#16
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
#17
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...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28187291/the-principles-of-engineering-immune-cells-to-treat-cancer
#18
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
#19
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
#20
Carlos Alberto Fajardo, Sonia Guedan, Luis Alfonso 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 that were armed with bispecific T-cell-engager (BiTE) antibodies...
April 15, 2017: Cancer Research
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