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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/28202953/fully-human-cd19-specific-chimeric-antigen-receptors-for-t-cell-therapy
#2
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/28202780/erratum-for-the-report-molecular-remission-of-infant-b-all-after-infusion-of-universal-talen-gene-edited-car-t-cells-by-w-qasim-h-zhan-s-samarasinghe-s-adams-p-amrolia-s-stafford-k-butler-c-rivat-g-wright-k-somana-s-ghorashian-d-pinner-g-ahsan-k-gilmour-g-lucchini
#3
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#4
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28199983/a-versatile-system-for-rapid-multiplex-genome-edited-car-t-cell-generation
#5
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/28197840/computational-study-of-th-4-and-np-4-hydration-and-hydrolysis-of-th-4-from-first-principles
#6
Davi H T Amador, Julio R Sambrano, Ricardo Gargano, Luiz Guilherme M de Macedo
The aqueous solvation of Th and Np in the IV oxidation state was examined using cluster models generated by Monte Carlo simulations and density functional theory embedded within the COSMO continuum model to approximate the effect of bulk water. Our results suggest that the coordination number (CN) for both Th(IV) and NP(IV) should be 9, in accordance to some experimental and theoretical results from the literature. The structural values for average oxygen-metal distances are within 0.01 Å compared to experimental data, and also within the experimental error...
March 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28193777/tracing-the-path-of-car-t-cells
#7
(no author information available yet)
Adding a radioactive tag to CAR T cells has allowed these engineered cells to be monitored as they home in on brain tumors in patients. The technique could help promote a deeper understanding of why this immunotherapy isn't more broadly effective, and why resistance sometimes develops.
February 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28193774/universal-car-t-cells-successfully-treat-leukemia
#8
(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/28193532/age-dependent-atypicalities-in-body-and-face-sensitive-activation-of-the-eba-and-ffa-in-individuals-with-asd
#9
Yuko Okamoto, Hirotaka Kosaka, Ryo Kitada, Ayumi Seki, Hiroki C Tanabe, Masamichi J Hayashi, Takanori Kochiyama, Daisuke N Saito, Hisakazu T Yanaka, Toshio Munesue, Makoto Ishitobi, Masao Omori, Yuji Wada, Hidehiko Okazawa, Tatsuya Koeda, Norihiro Sadato
Individuals with autism spectrum disorder (ASD) have difficuly in recognizing bodies and faces, which are more pronounced in children than adults. If such difficulties originate from dysfunction of the extrastriate body area (EBA) and the fusiform face area (FFA), activation in these regions might be more atypical in children than in adults. We preformed functional magnetic resonance imaging while children and adults with ASD and age-matched typically developed (TD) individuals observed face, body, car, and scene...
February 10, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28190461/detection-of-mycobacterium-chelonae-mycobacterium-abscessus-group-and-mycobacterium-fortuitum-complex-by-a-multiplex-real-time-pcr-directly-from-clinical-samples-using-the-bd-max-system
#10
Talita T Rocchetti, Suzane Silbert, Alicia Gostnell, Carly Kubasek, Antonio C Campos Pignatari, Raymond Widen
A new multiplex PCR test was designed to detect Mycobacterium chelonae, Mycobacterium abscessus group, and Mycobacterium fortuitum complex on the BD MAX System. A total of 197 clinical samples previously submitted for mycobacterial culture were tested using the new protocol. Samples were first treated with proteinase K, and then each sample was inoculated into the BD MAX Sample Buffer Tube. Extraction and multiplex PCR were performed by the BD MAX System, using the BD MAX ExK TNA-3 extraction kit and BD TNA Master Mix, along with specific in-house designed primers and probes for each target...
March 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28188669/orthogonal-comparison-of-molecular-signatures-of-kidney-transplants-with-subclinical-and-clinical-acute-rejection-equivalent-performance-is-agnostic-to-either-technology-or-platform
#11
S M Kurian, E Velazquez, R Thompson, T Whisenant, S Rose, N Riley, F Harrison, T Gelbart, J J Friedewald, J Charrette, S Brietigam, J Peysakhovich, M R First, M M Abecassis, D R Salomon
We performed orthogonal technology comparisons of concurrent peripheral blood and biopsy tissue samples from 69 kidney transplant recipients, who underwent a comprehensive algorithm-driven clinical phenotyping. The sample cohort included patients with normal protocol biopsies and stable transplant function (TX, n=25), subclinical acute rejection (subAR, n=23), and clinical acute rejection (cAR, n=21). Comparisons between microarray and RNA sequencing (RNA-seq) signatures were performed, demonstrating a strong correlation between the blood and tissue compartments for both technology platforms...
February 11, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28187946/inducible-caspase-9-selectively-modulates-the-toxicities-of-cd19-specific-chimeric-antigen-receptor-modified-t-cells
#12
Iulia Diaconu, Brandon Ballard, Ming Zhang, Yuhui Chen, John West, Gianpietro Dotti, Barbara Savoldo
Immunotherapy with T cells expressing the chimeric antigen receptor (CAR) specific for the CD19 antigen (CD19.CAR-Ts) is a very effective treatment in B cell lymphoid malignancies. However, B cell aplasia and cytokine release syndrome (CRS) secondary to the infusion of CD19.CAR-Ts remain significant drawbacks. The inclusion of safety switches into the vector encoding the CAR is seen as the safest method to terminate the effects of CD19.CAR-Ts in case of severe toxicities or after achieving long-term sustained remissions...
February 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28187291/the-principles-of-engineering-immune-cells-to-treat-cancer
#13
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/28186088/current-status-of-immunotherapy-for-gastrointestinal-stromal-tumor
#14
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/28183713/vaccination-targeting-native-receptors-to-enhance-the-function-and-proliferation-of-chimeric-antigen-receptor-car-modified-t-cells
#15
Miyuki Tanaka, Haruko Tashiro, Bilal Omer, Natasha Lapteva, Jun Ando, Minhtran Ngo, Birju Mehta, Gianpietro Dotti, Paul R Kinchington, Ann M Leen, Claudia Rossig, Cliona M Rooney
PURPOSE: The multiple mechanisms used by solid tumors to suppress tumor-specific immune responses are a major barrier to the success of adoptively-transferred tumor-specific T-cells. Since viruses induce potent innate and adaptive immune responses, we hypothesized that the immunogenicity of viruses could be harnessed for the treatment of solid tumors if virus-specific T-cells (VSTs) were modified with tumor-specific chimeric antigen receptors (CARs). We tested this hypothesis using VZV-specific T-cells (VZVSTs) expressing a CAR for GD2, a disialoganglioside expressed on neuroblastoma and certain other tumors, since the live-attenuated VZV vaccine could be used for in vivo stimulation...
February 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28173706/insb-nanowires-with-built-in-gaxin1-xsb-tunnel-barriers-for-majorana-devices
#16
Diana Car, Sonia Conesa-Boj, Hao Zhang, Roy L M Op Het Veld, Michiel W A de Moor, Elham M T Fadaly, Önder Gül, Sebastian Kölling, Sebastien R Plissard, Vigdis Toresen, Michael T Wimmer, Kenji Watanabe, Takashi Taniguchi, Leo P Kouwenhoven, Erik P A M Bakkers
Majorana zero modes (MZMs), prime candidates for topological quantum bits, are detected as zero bias conductance peaks (ZBPs) in tunneling spectroscopy measurements. Implementation of a narrow and high tunnel barrier in the next generation of Majorana devices can help to achieve the theoretically predicted quantized height of the ZBP. We propose a material-oriented approach to engineer a sharp and narrow tunnel barrier by synthesizing a thin axial segment of GaxIn1-xSb within an InSb nanowire. By varying the precursor molar fraction and the growth time, we accurately control the composition and the length of the barriers...
February 8, 2017: Nano Letters
https://www.readbyqxmd.com/read/28170385/exhausting-alloreactivity-of-donor-derived-car-t-cells
#17
Maksim Mamonkin, Helen E Heslop
No abstract text is available yet for this article.
February 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28165340/targeting-the-adenosine-2a-receptor-enhances-chimeric-antigen-receptor-t-cell-efficacy
#18
Paul A Beavis, Melissa A Henderson, Lauren Giuffrida, Jane K Mills, Kevin Sek, Ryan S Cross, Alexander J Davenport, Liza B John, Sherly Mardiana, Clare Y Slaney, Ricky W Johnstone, Joseph A Trapani, John Stagg, Sherene Loi, Lev Kats, David Gyorki, Michael H Kershaw, Phillip K Darcy
Chimeric antigen receptor (CAR) T cells have been highly successful in treating hematological malignancies, including acute and chronic lymphoblastic leukemia. However, treatment of solid tumors using CAR T cells has been largely unsuccessful to date, partly because of tumor-induced immunosuppressive mechanisms, including adenosine production. Previous studies have shown that adenosine generated by tumor cells potently inhibits endogenous antitumor T cell responses through activation of adenosine 2A receptors (A2ARs)...
February 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28162024/immunotherapeutic-strategies-for-the-treatment-of-renal-cell-carcinoma-where-will-we-go
#19
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/28160417/nmr-structure-based-optimization-of-staphylococcus-aureus-sortase-a-pyridazinone-inhibitors
#20
Albert H Chan, Sung Wook Yi, Ethan M Weiner, Brendan R Amer, Christopher K Sue, Jeff Wereszczynski, Carly A Dillen, Silvia Senese, Jorge Z Torres, J Andrew McCammon, Lloyd S Miller, Michael E Jung, Robert T Clubb
Staphylococcus aureus is a leading cause of hospital-acquired infections in the United States and is a major health concern as methicillin-resistant S. aureus (MRSA) and other antibiotic resistant strains are common. Compounds that inhibit the S. aureus sortase (SrtA) cysteine transpeptidase may function as potent anti-infective agents as this enzyme attaches virulence factors to the bacterial cell wall. While a variety of SrtA inhibitors have been discovered, the vast majority of these small molecules have not been optimized using structure-based approaches...
February 3, 2017: Chemical Biology & Drug Design
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