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CAR T-Cells

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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/28193777/tracing-the-path-of-car-t-cells
#6
(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
#7
(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/28187946/inducible-caspase-9-selectively-modulates-the-toxicities-of-cd19-specific-chimeric-antigen-receptor-modified-t-cells
#8
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
#9
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
#10
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
#11
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/28170385/exhausting-alloreactivity-of-donor-derived-car-t-cells
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28153859/high-response-to-anti-cd19-car-therapy-in-dlbcl
#16
(no author information available yet)
According to an interim analysis of phase II data from a study of the anti-CD19 chimeric antigen receptor T-cell therapy KTE-C19, 76% of 51 patients with diffuse large B-cell lymphoma responded to the treatment; 47% had a complete response. After 3 months, 33% continued to experience a complete response.
February 2, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28153101/viral-vector-malaria-vaccines-induce-high-level-t-cell-and-antibody-responses-in-west-african-children-and-infants
#17
Carly M Bliss, Abdoulie Drammeh, Georgina Bowyer, Guillaume S Sanou, Ya Jankey Jagne, Oumarou Ouedraogo, Nick J Edwards, Casimir Tarama, Nicolas Ouedraogo, Mireille Ouedraogo, Jainaba Njie-Jobe, Amidou Diarra, Muhammed O Afolabi, Alfred B Tiono, Jean Baptiste Yaro, Uche J Adetifa, Susanne H Hodgson, Nicholas A Anagnostou, Rachel Roberts, Christopher J A Duncan, Riccardo Cortese, Nicola K Viebig, Odile Leroy, Alison M Lawrie, Katie L Flanagan, Beate Kampmann, Egeruan B Imoukhuede, Sodiomon B Sirima, Kalifa Bojang, Adrian V S Hill, Issa Nébié, Katie J Ewer
Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8(+) T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28143740/engineering-hiv-resistant-anti-hiv-chimeric-antigen-receptor-t-cells
#18
Malika Hale, Taylor Mesojednik, Guillermo S Romano Ibarra, Jaya Sahni, Alison Bernard, Karen Sommer, Andrew M Scharenberg, David J Rawlings, Thor A Wagner
The treatment or cure of HIV infection by cell and gene therapy has been a goal for decades. Recent advances in both gene editing and chimeric antigen receptor (CAR) technology have created new therapeutic possibilities for a variety of diseases. Broadly neutralizing monoclonal antibodies (bNAbs) with specificity for the HIV envelope glycoprotein provide a promising means of targeting HIV-infected cells. Here we show that primary human T cells engineered to express anti-HIV CARs based on bNAbs (HIVCAR) show specific activation and killing of HIV-infected versus uninfected cells in the absence of HIV replication...
January 28, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28143567/allogeneic-cd19-car-t-cell-infusion-after-allogeneic-hematopoietic-stem-cell-transplantation-in-b-cell-malignancies
#19
REVIEW
Jun Liu, Jiang F Zhong, Xi Zhang, Cheng Zhang
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the cornerstone in treatment of hematological malignancies. However, relapse of the hematological disease after allo-HSCT remains a challenge and is associated with poor long-term survival. Chimeric antigen receptor redirected T cells (CAR-T cells) can lead to disease remission in patients with relapsed/refractory hematological malignancies. However, the therapeutic window for infusion of CAR-T cells post allo-HSCT and its efficacy are debatable...
January 31, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28137279/interplay-between-ccr7-and-notch1-axes-promotes-stemness-in-mmtv-pymt-mammary-cancer-cells
#20
Sarah T Boyle, Krystyna A Gieniec, Carly E Gregor, Jessica W Faulkner, Shaun R McColl, Marina Kochetkova
BACKGROUND: Breast cancer is the major cause of cancer-related mortality in women. It is thought that quiescent stem-like cells within solid tumors are responsible for cancer maintenance, progression and eventual metastasis. We recently reported that the chemokine receptor CCR7, a multi-functional regulator of breast cancer, maintains the stem-like cell population. METHODS: This study used a combination of molecular and cellular assays on primary mammary tumor cells from the MMTV-PyMT transgenic mouse with or without CCR7 to examine the signaling crosstalk between CCR7 and Notch pathways...
January 31, 2017: Molecular Cancer
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