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https://www.readbyqxmd.com/read/28805662/clinical-and-immunological-responses-after-cd30-specific-chimeric-antigen-receptor-redirected-lymphocytes
#1
Carlos A Ramos, Brandon Ballard, Huimin Zhang, Olga Dakhova, Adrian P Gee, Zhuyong Mei, Mrinalini Bilgi, Meng-Fen Wu, Hao Liu, Bambi Grilley, Catherine M Bollard, Bill H Chang, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop, Gianpietro Dotti, Barbara Savoldo
BACKGROUND: Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS: We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28804691/combination-of-celecoxib-celebrex-%C3%A2-and-cd19-car-redirected-ctl-immunotherapy-for-the-treatment-of-b-cell-non-hodgkin-s-lymphomas
#2
REVIEW
Tam Nm Dinh, Alexandra S Onea, Ali R Jazirehi
The nonsteroidal anti-inflammatory drug (NSAID) Celecoxib (Celebrex(®)) received Food and Drug Administration (FDA) approval in 1998 for treatment of osteoarthritis and rheumatoid arthritis, and in recent years, its use has been extended to various types of malignancies, such as breast, colon, and urinary cancers. To maintain the survival of malignant B cells, non-Hodgkin's Lymphoma (NHL) is highly dependent on inflammatory microenvironment, and is inhibited by celecoxib. Celecoxib hinders tumor growth interacting with various apoptotic genes, such as cyclooxygenase-2 (Cox-2), B-cell lymphoma 2 (Bcl-2) family, phosphor-inositide-3 kinase/serine-threonine-specific protein kinase (PI3K/Akt), and inhibitors of apoptosis proteins (IAP) family...
2017: American Journal of Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28803861/long-duration-complete-remissions-of-diffuse-large-b-cell-lymphoma-after-anti-cd19-chimeric-antigen-receptor-t%C3%A2-cell-therapy
#3
James N Kochenderfer, Robert P T Somerville, Tangying Lu, James C Yang, Richard M Sherry, Steven A Feldman, Lori McIntyre, Adrian Bot, John Rossi, Norris Lam, Steven A Rosenberg
T cells expressing anti-CD19 chimeric antigen receptors (CARs) can induce complete remissions (CRs) of diffuse large B cell lymphoma (DLBCL). The long-term durability of these remissions is unknown. We administered anti-CD19 CAR T cells preceded by cyclophosphamide and fludarabine conditioning chemotherapy to patients with relapsed DLBCL. Five of the seven evaluable patients obtained CRs. Four of the five CRs had long-term durability with durations of remission of 56, 51, 44, and 38 months; to date, none of these four cases of lymphomas have relapsed...
July 13, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28801306/inducible-activation-of-myd88-and-cd40-in-car-t-cells-results-in-controllable-and-potent-antitumor-activity-in-preclinical-solid-tumor-models
#4
Melinda Mata, Claudia Gerken, Phuong Nguyen, Giedre Krenciute, David M Spencer, Stephen Gottschalk
Adoptive immunotherapy with T-cells expressing chimeric antigen receptors (CARs) has had limited success for solid tumors in early phase clinical studies. We reasoned that introducing into CAR T-cells an inducible co-stimulatory (iCO) molecule consisting of a chemical inducer of dimerization (CID)-binding domain and the MyD88 and CD40 signaling domains would improve and control CAR T-cell activation. In the presence of CID, T-cells expressing HER2-CARζ and a MyD88/CD40-based iCO molecule (HER2ζ.iCO T-cells) had superior T-cell proliferation, cytokine production, and ability to sequentially kill targets in vitro relative to HER2ζ...
August 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28790870/repository-corticotropin-injection-as-adjunctive-therapy-in-patients-with-rheumatoid-arthritis-who-have-failed-previous-therapies-with-at-least-three-different-modes-of-action
#5
Theresa Gillis, Megan Crane, Carly Hinkle, Nathan Wei
OBJECTIVE: Many types of treatment are available for patients with rheumatoid arthritis (RA), however, some patients fail to achieve remission. This report aims to determine the safety and efficacy of using repository corticotropin injection (RCI) as an adjunctive therapy in patients with RA refractory to at least three therapeutics with different mechanisms of action. METHOD: In this open-label, interventional, single-group study, patients received 80 U RCI twice weekly via subcutaneous injection over 12 weeks...
2017: Open Access Rheumatology: Research and Reviews
https://www.readbyqxmd.com/read/28790513/the-jeremiah-metzger-lecture-cancer-in-the-twenty-first-century-an-inside-view-from-an-outsider
#6
Edward J Benz
Cancer is not a single disease. The term refers to literally hundreds of illnesses sharing common features: inappropriate proliferation of imperfectly differentiated cell types, invasion of nearby vital structures, and spread to distant sites (metastasis). Invasiveness and metastasis distinguish cancers from benign tumors such as fibroids and meningiomas. Yet, each type is distinct, possessed of defining morphologic, histologic, biochemical, and genomic features that have allowed oncologists to develop a nosology that guides diagnosis and therapy...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28771104/-atypical-car-t-cells-nkg2d-and-erb-b-as-examples-of-natural-receptor-ligands-to-target-recalcitrant-solid-tumors
#7
David E Gilham, John Maher
Chimeric antigen receptor (CAR) T-cell therapy has recently been recommended for approval for certain B-cell malignancies bringing the approach closer to mainstream cancer treatment. This rapid rise to prominence has been driven by impressive clinical results and the means to successfully commercialize the approach now being actively pursued. The current success of CAR T cells in B-cell malignancies relies upon the absolute lineage specificity of the CD19 antigen. CARs can also be targeted using non-antibody approaches, including the use of receptors and ligands to provide target specificity that have different specificities and binding kinetics...
August 3, 2017: Immunotherapy
https://www.readbyqxmd.com/read/28771103/overcoming-barriers-of-car-t-cell-therapy-in-patients-with-mesothelin-expressing-cancers
#8
Mark H O'Hara, Caitlin Stashwick, Gabriela Plesa, Janos L Tanyi
One obstacle to the application of immunotherapy to solid malignancies is to overcome the existing tolerance to self-antigens. Vaccine strategies aimed at harnessing endogenous antitumor T cells are limited by the T-cell receptor repertoire, which can be detected within the thymus as central tolerance or rendered nonfunctional by post-thymic mechanisms of peripheral tolerance. Adoptive immunotherapy can overcome these obstacles, since therapeutically effective T cells can be engineered to recognize tumors. Continued advancements in novel treatments, including immunotherapy, in solid malignancies are imperative...
August 3, 2017: Immunotherapy
https://www.readbyqxmd.com/read/28770590/delivering-hiv-care-in-challenging-operating-environments-the-msf-experience-towards-differentiated-models-of-care-for-settings-with-multiple-basic-health-care-needs
#9
REVIEW
Charles Ssonko, Lucia Gonzalez, Anita Mesic, Marcio Silveira da Fonseca, Jay Achar, Nadia Safar, Beatriz Martin, Sidney Wong, Esther C Casas
INTRODUCTION: Countries in the West and Central African regions struggle to offer quality HIV care at scale, despite HIV prevalence being relatively low. In these challenging operating environments, basic health care needs are multiple, systems are highly fragile and conflict disrupts health care. Médecins Sans Frontières (MSF) has been working to integrate HIV care in basic health services in such settings since 2000. We review the implementation of differentiated HIV care and treatment approaches in MSF-supported programmes in South Sudan (RoSS), Central African Republic (CAR) and Democratic Republic of Congo (DRC)...
July 21, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28770463/joint-snmmi-asnc-expert-consensus-document-on-the-role-of-18-f-fdg-pet-ct-in-cardiac-sarcoid-detection-and-therapy-monitoring
#10
Panithaya Chareonthaitawee, Rob S Beanlands, Wengen Chen, Sharmila Dorbala, Edward J Miller, Venkatesh L Murthy, David H Birnie, Edward S Chen, Leslie T Cooper, Roderick H Tung, Eric S White, Salvador Borges-Neto, Marcelo F Di Carli, Robert J Gropler, Terrence D Ruddy, Thomas H Schindler, Ron Blankstein
No abstract text is available yet for this article.
August 2, 2017: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
https://www.readbyqxmd.com/read/28765228/joint-snmmi-asnc-expert-consensus-document-on-the-role-of-18-f-fdg-pet-ct-in-cardiac-sarcoid-detection-and-therapy-monitoring
#11
Panithaya Chareonthaitawee, Rob S Beanlands, Wengen Chen, Sharmila Dorbala, Edward J Miller, Venkatesh L Murthy, David H Birnie, Edward S Chen, Leslie T Cooper, Roderick H Tung, Eric S White, Salvador Borges-Neto, Marcelo F Di Carli, Robert J Gropler, Terrence D Ruddy, Thomas H Schindler, Ron Blankstein
No abstract text is available yet for this article.
August 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28765140/clinical-development-of-car-t-cells-challenges-and-opportunities-in-translating-innovative-treatment-concepts
#12
REVIEW
Jessica Hartmann, Martina Schüßler-Lenz, Attilio Bondanza, Christian J Buchholz
Chimeric antigen receptor (CAR) T cell therapy, together with checkpoint inhibition, has been celebrated as a breakthrough technology due to the substantial benefit observed in clinical trials with patients suffering from relapsed or refractory B-cell malignancies. In this review, we provide a comprehensive overview of the clinical trials performed so far worldwide and analyze parameters such as targeted antigen and indication, CAR molecular design, CAR T cell manufacturing, anti-tumor activities, and related toxicities...
August 1, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28764981/promises-and-limitations-of-nanoparticles-in-the-era-of-cell-therapy-example-with-cd19-targeting-chimeric-antigen-receptor-car-modified-t-cells
#13
Hélène Jakobczyk, Flavien Sciortino, Soizic Chevance, Fabienne Gauffre, Marie-Bérengère Troadec
A number of nanoparticles has been developed by chemists for biomedical applications to meet imaging and targeting needs. In parallel, adoptive T therapy with chimeric antigen receptor engineered T cells (CART cells) has recently held great promise in B-cell malignancy treatments thanks to the development of anti-CD19 CAR T cells. Indeed, CD19 is a reliable B cell marker and a validated target protein for therapy. In this perspective article, we propose to discuss the advantages, limits and challenges of nanoparticles and CAR T cells, focusing on CD19 targeting objects: anti-CD19 nanoparticles and anti-CD19 CAR T cells, because those genetically-modified cells are the most widely developed in clinical setting...
July 29, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28763427/safety-of-outpatient-parenteral-antimicrobial-therapy-in-children
#14
Priyanka Fernandes, Carly Milliren, Helen M Mahoney-West, Laura Schwartz, Catherine S Lachenauer, Mari M Nakamura
BACKGROUND AND OBJECTIVE: Outpatient parenteral antimicrobial therapy (OPAT) provides numerous benefits but may pose unique risks in children. We aimed to determine rates of OPAT antimicrobial- and intravenous-access-related complications and their associations with specific antimicrobials and type of intravenous access in pediatric patients. METHODS: Observational cohort study of patients receiving OPAT from 8/2008 to 5/2015 cared for by the Infectious Diseases service at a tertiary children's hospital...
July 31, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28757080/a-fusion-receptor-as-a-safety-switch-detection-and-purification-biomarker-for-adoptive-transferred-t-cells
#15
Xiuqi Wu, Bizhi Shi, Jiqin Zhang, Zhimin Shi, Shengmeng Di, Minliang Fan, Huiping Gao, Hai Wang, Jianren Gu, Hua Jiang, Zonghai Li
The incorporation of an endogenous safety switch represents a rational strategy for the control of toxicities following the administration of adoptive T cell therapies. An ideal safety switch should be capable of depleting the transferred T cells with minimal injury to normal tissues. We generated a fusion receptor by engineering a cryptic 806 epitope of human epidermal growth factor receptor (EGFR) into the N terminus of the full-length human folate receptor 1 (FOLR1), designated as FR806. The expression of FR806 allows transduced T cells to be targeted with CH12, a monoclonal antibody recognizing the 806 epitope, but not wild-type EGFR in healthy tissues...
July 3, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28755873/chimeric-antigen-receptor-t-cell-therapy-for-glioblastoma
#16
REVIEW
Analiz Rodriguez, Christine Brown, Behnam Badie
Chimeric antigen receptor (CAR) T-cell therapy has shown great promise in the treatment of hematological disease, and its utility for treatment of solid tumors is beginning to unfold. Glioblastoma continues to portend a grim prognosis and immunotherapeutic approaches are being explored as a potential treatment strategy. Identification of appropriate glioma-associated antigens, barriers to cell delivery, and presence of an immunosuppressive microenvironment are factors that make CAR T-cell therapy for glioblastoma particularly challenging...
July 15, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28755872/new-approaches-for-the-enhancement-of-chimeric-antigen-receptors-for-the-treatment-of-hiv
#17
REVIEW
Mayra A Carrillo, Anjie Zhen, Jerome A Zack, Scott G Kitchen
HIV infection continues to be a life-long chronic disease in spite of the success of antiretroviral therapy (ART) in controlling viral replication and preventing disease progression. However, because of the high cost of treatment, severe side effects, and inefficiency in curing the disease with ART, there is a call for alternative therapies that will provide a functional cure for HIV. Cytotoxic T lymphocytes (CTLs) are vital in the control and clearance of viral infections and therefore immune-based therapies have attempted to engineer HIV-specific CTLs that would be able to clear the infection from the body...
July 14, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28754600/building-blocks-for-institutional-preparation-of-ctl019-delivery
#18
REVIEW
Joseph McGuirk, Edmund K Waller, Muna Qayed, Sunil Abhyankar, Solveig Ericson, Peter Holman, Christopher Keir, G Douglas Myers
Chimeric antigen receptor (CAR) T-cell therapy is an investigational immunocellular therapy that reprograms a patient's cytotoxic T cells to engage and eliminate malignant cells. CAR T-cell therapies targeting the CD19 antigen have demonstrated high efficacy in clinical trials for patients with B-cell malignancies and may potentially be available on a broader scale in the future. CAR T-cell therapy begins with the collection of a sufficient number of T cells from a patient's peripheral blood through leukapheresis...
July 25, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28752313/the-elusive-role-of-myocardial-perfusion-imaging-in-stable-ischemic-heart-disease-is-ischemia-the-answer
#19
Joe X Xie, David E Winchester, Lawrence M Phillips, Rory Hachamovitch, Daniel S Berman, Ron Blankstein, Marcelo F Di Carli, Todd D Miller, Mouaz H Al-Mallah, Leslee J Shaw
The assessment of ischemia through myocardial perfusion imaging (MPI) is widely accepted as an index step in the diagnostic evaluation of stable ischemic heart disease (SIHD). Numerous observational studies have characterized the prognostic significance of ischemia extent and severity. However, the role of ischemia in directing downstream SIHD care including coronary revascularization has remained elusive as reductions in ischemic burden have not translated to improved clinical outcomes in randomized trials...
July 27, 2017: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
https://www.readbyqxmd.com/read/28751490/panel-oks-car-t-therapy-for-leukemia
#20
(no author information available yet)
An expert panel recommended approval of Novartis's experimental chimeric antigen T-cell therapy, tisagenlecleucel, for children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia. The therapy would be the first of its kind approved for cancer and has the potential to transform standard of care for advanced blood cancers.
July 27, 2017: Cancer Discovery
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