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https://www.readbyqxmd.com/read/29930315/author-correction-integrating-oncolytic-viruses-in-combination-cancer-immunotherapy
#1
Praveen K Bommareddy, Megha Shettigar, Howard L Kaufman
In the initially published version of this article online in advance of print, a reference (Ajina, A. & Maher, J. Prospects for combined use of oncolytic viruses and CAR T-cells. J. Immunother. Cancer 5, 90 (2017)) was omitted in error from the following sentence: "The ability of oncolytic viruses to increase the expression of MHC class I molecules by cancer cells is also predicted to enhance ACT with TILs or TCR-engineered and chimeric antigen receptor (CAR) T cells that target tumour-specific antigens"...
June 21, 2018: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/29928397/construction-of-an-anti-programmed-death-ligand-1-chimeric-antigen-receptor-and-determination-of-its-antitumor-function-with-transduced-cells
#2
Jiasen Xie, Zishan Zhou, Shunchang Jiao, Xiaokun Li
A chimeric antigen receptor (CAR) is a type of fusion protein that comprises an antigen-recognition domain and signaling domains. In the present study, a programmed death-ligand 1 (PD-L1)-specific CAR, comprised of a single-chain variable fragment (scFv) derived from a monoclonal antibody, co-stimulatory domains of cluster of differentiation (CD) 28 and 4-1BB and a T-cell-activation domain derived from CD3ζ, was designed. The construction was cloned and packaged into the lentiviral vector pLVX. Flow cytometry confirmed that peripheral blood mononuclear cells were efficiently transduced and that the CAR was successfully expressed on T cells...
July 2018: Oncology Letters
https://www.readbyqxmd.com/read/29925499/non-viral-rna-chimeric-antigen-receptor-modified-t-cells-in-patients-with-hodgkin-lymphoma
#3
Jakub Svoboda, Susan R Rheingold, Saar I Gill, Stephan A Grupp, Simon F Lacey, Irina Kulikovskaya, Megan M Suhoski, J Joseph Melenhorst, Brandon Loudon, Anthony R Mato, Sunita Dwivedy Nasta, Daniel J Landsburg, Matthew R Youngman, Bruce L Levine, David L Porter, Carl H June, Stephen J Schuster
Chimeric antigen receptor (CAR) modified T cells are being investigated in many settings including classical Hodgkin lymphoma (cHL). The unique biology of cHL, characterized by scant Hodgkin and Reed-Sternberg (HRS) cells within an immunosuppressive tumor microenvironment (TME), may pose challenges for cellular therapies directly targeting antigens expressed on HRS. We hypothesized that eradicating CD19 positive (+) B cells within the TME and the putative circulating CD19+ HRS clonotypic cells using anti-CD19 directed CAR modified T cells (CART19) may indirectly affect HRS cells, which do not express CD19...
June 20, 2018: Blood
https://www.readbyqxmd.com/read/29920129/activity-of-anti-cd19-chimeric-antigen-receptor-t-cells-against-b-cell-lymphoma-is-enhanced-by-antibody-targeted-interferon-alpha
#4
Patricia A Young, Reiko E Yamada, Kham R Trinh, Alex Vasuthasawat, Satiro De Oliveira, Douglas H Yamada, Sherie L Morrison, John M Timmerman
An important emerging form of immunotherapy targeting B cell malignancies is chimeric antigen receptor (CAR) T cell therapy. Despite encouraging response rates of anti-CD19 CAR T cell therapy in B cell lymphomas, limited durability of response necessitates further study to potentiate CAR T cell efficacy. Antibody-targeted interferon (IFN) therapy is a novel approach in immunotherapy. Given the ability of IFNs to promote T cell activation and survival, target cell recognition, and cytotoxicity, we asked whether antibody-targeted IFN could enhance the antitumor effects of anti-CD19 CAR T cells...
June 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29914976/translating-anti-cd19-car-t-cell-therapy-into-clinical-practice-for-relapsed-refractory-diffuse-large-b-cell-lymphoma
#5
Victor A Chow, Mazyar Shadman, Ajay K Gopal
Chimeric antigen receptor (CAR) T-cells demonstrate efficacy in B-cell malignancies, leading to FDA approval of axicaptagene ciloleucel in October 2017 and tisagenlecleucel in May 2018 for large B-cell lymphomas after two prior lines of therapy. Durable remissions are seen in 30-40% of study-treated patients, but unique toxicities of cytokine release syndrome and neurotoxicity require administration in specialized centers. This article reviews the data to-date within the context of current diffuse large B-cell lymphoma management, focusing on axicaptagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel...
June 18, 2018: Blood
https://www.readbyqxmd.com/read/29914571/targeting-adenosine-for-cancer-immunotherapy
#6
Robert D Leone, Leisha A Emens
Immune checkpoint antagonists (CTLA-4 and PD-1/PD-L1) and CAR T-cell therapies generate unparalleled durable responses in several cancers and have firmly established immunotherapy as a new pillar of cancer therapy. To extend the impact of immunotherapy to more patients and a broader range of cancers, targeting additional mechanisms of tumor immune evasion will be critical. Adenosine signaling has emerged as a key metabolic pathway that regulates tumor immunity. Adenosine is an immunosuppressive metabolite produced at high levels within the tumor microenvironment...
June 18, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29910620/axicabtagene-ciloleucel-kte-c19-an-anti-cd19-car-t-therapy-for-the-treatment-of-relapsed-refractory-aggressive-b-cell-non-hodgkin-s-lymphoma
#7
REVIEW
Michael D Jain, Christina A Bachmeier, Vania H Phuoc, Julio C Chavez
Adoptive T-cell immunotherapy is a rapidly growing field and is shifting the paradigm of clinical cancer treatment. Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor T-cell therapy that was initially developed at the National Cancer Institute and has recently been commercially approved by the US Food and Drug Administration for relapsed or refractory aggressive non-Hodgkin's lymphomas including diffuse large B-cell lymphoma and its variants. The ZUMA-1 Phase I and II clinical trials formed the basis of the US Food and Drug Administration approval of this product, and we discuss the particulars of the clinical trials and the pharmacology of axi-cel...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29910179/autologous-cd19-targeted-car-t-cells-in-patients-with-residual-cll-following-initial-purine-analog-based-therapy
#8
Mark B Geyer, Isabelle Rivière, Brigitte Sénéchal, Xiuyan Wang, Yongzeng Wang, Terence J Purdon, Meier Hsu, Sean M Devlin, Elizabeth Halton, Nicole Lamanna, Jurgen Rademaker, Michel Sadelain, Renier J Brentjens, Jae H Park
Patients with residual chronic lymphocytic leukemia (CLL) following initial purine analog-based chemoimmunotherapy exhibit a shorter duration of response and may benefit from novel therapeutic strategies. We and others have previously described the safety and efficacy of autologous T cells modified to express anti-CD19 chimeric antigen receptors (CARs) in patients with relapsed or refractory B cell acute lymphoblastic leukemia and CLL. Here we report the use of CD19-targeted CAR T cells incorporating the intracellular signaling domain of CD28 (19-28z) as a consolidative therapy in 8 patients with residual CLL following first-line chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab...
June 14, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29909918/advances-in-the-use-of-natural-receptor-or-ligand-based-chimeric-antigen-receptors-cars-in-haematologic-malignancies
#9
REVIEW
Joana M Murad, David J Graber, Charles L Sentman
Chimeric antigen receptors (CAR)-T cell therapy has recently made promising advances towards treatment of B-cell malignancies. This approach makes use of an antibody-derived single chain variable fragment (scFv)-based CAR to target the CD19 antigen. Currently scFvs are the most common strategy for creation of CARs, but tumor cells can also be targeted using non-antibody based approaches with designs focused on the interaction between natural receptors and their ligands. This emerging strategy has been used in unique ways to target multiple tumor types, including solid and haematological malignancies...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909917/off-the-shelf-t-cell-therapies-for-hematologic-malignancies
#10
REVIEW
Bruce J McCreedy, Vladimir V Senyukov, Kim T Nguyen
Adoptive transfer of autologous CAR-T cells can induce durable remissions in patients with relapsed/refractory hematologic malignancies. However, multiple challenges exist for manufacturing CAR-T cells from patients with advanced disease including inability to manufacture a product, disease progression or death while waiting for the CAR-T product to be available, and heterogeneity among autologous CAR-T products that contributes to unpredictable and variable clinical activity. Healthy donor T cells can provide a source for production of universal CAR-T cells when combined with gene editing to prevent expression of endogenous TCRs and avoid generation of GvHD in HLA mismatched recipients...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909916/toxicities-associated-with-immunotherapies-for-hematologic-malignancies
#11
REVIEW
Mark B Leick, Marcela V Maus
Immunotherapy has generated tremendous hope for patients with cancer that is refractory to standard approaches. Hematologic malignancies have taken the lead in harnessing the most recent advances in cell-based immunotherapies, such as CAR T cells, and some patients have achieved durable remissions. However, these T-cell-engaging therapies are associated with a new set of toxicities which need to be managed by caretakers, oncologists, nurses, and healthcare staff. In this review we provide an overview of the toxicity of some of these revolutionary agents including bispecific T cell engagers, checkpoint inhibitors, chimeric antigen receptor T-cells...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909915/cars-and-other-t-cell-therapies-for-mm-the-clinical-experience
#12
REVIEW
Sophia Danhof, Michael Hudecek, Eric L Smith
Harnessing the endogenous immune system to eliminate malignant cells has long been an intriguing approach. After considerable success in the treatment of B-cell acute lymphoblastic leukemia, chimeric antigen receptor (CAR)-modified T cells have entered early clinical evaluation in the field of multiple myeloma (MM). The choice of suitable non-CD19 target antigens is challenging and a variety of myeloma-associated surface molecules have been under preclinical investigation. Most recent clinical protocols have focused on targeting B-cell maturation antigen (BCMA), and early results are promising...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909914/car-t-cell-therapy-for-b-cell-lymphomas
#13
REVIEW
Julio C Chavez, Frederick L Locke
B-cell non-Hodgkin's lymphoma (NHLs)is a very heterogonous malignancy with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) as the most common subtypes. Standard treatment with anti-CD20 based chemoimmunotherapy is usually very effective for disease control. However a significant proportion of patients with high-risk features (double hit lymphoma, transformed lymphomas or early relapses) will become refractory to standard therapies and will have limited alternatives for cure. Adoptive therapy with chimeric antigen receptor (CAR) T-cells is a new paradigm for effective treatment of poor prognosis lymphomas...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909913/gmp-car-t-cell-production
#14
REVIEW
Adrian P Gee
The clinical success achieved using CD19-directed CAR-T cells has stimulated many academic institutions to explore the feasibility of manufacturing these, and other CAR-T cells, in-house. This article reviews the issues that must be addressed in order to achieve this goal. It includes the manufacturing infrastructure, the regulatory environment, practical aspects of production, and the costs involved.
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909912/pre-clinical-development-of-chimeric-antigen-receptor-t-cell-immunotherapy-implications-of-design-for-efficacy-and-safety
#15
REVIEW
Leena Halim, Adam Ajina, John Maher
Following the landmark approvals by the United States Food and Drug Administration, the adoptive transfer of CD19-directed chimeric antigen receptor (CAR) T-cells has now entered mainstream clinical practice for patients with chemotherapy-resistant or refractory B-cell malignancies. These approvals have followed on from a prolonged period of pre-clinical evaluation, informing the design of clinical trials that have demonstrated unprecedented efficacy in this difficult to treat patient population. However, the delivery of autologous CAR-engineered T-cell therapy is complex, costly and not without significant risk...
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29909911/car-t-cells-immunologic-and-cellular-therapies-in-hematologic-malignancies
#16
EDITORIAL
Renier Brentjens, Marco L Davila
No abstract text is available yet for this article.
June 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29908946/effects-of-cryopreservation-on-chimeric-antigen-receptor-t-cell-functions
#17
Hao Xu, Wenyue Cao, Liang Huang, Min Xiao, Yang Cao, Lei Zhao, Na Wang, Jianfeng Zhou
Chimeric antigen receptor T (CART) cell therapy has emerged as a potentially curative "drug" for cancer treatment. Cryopreservation of CART cells is necessary for their clinical application. Systematic studies on the effects of cryopreservation on the antitumor function of CART cells are lacking. Therefore, we compared the phenotypes and functions of CART cells that were cryopreserved during ex vivo expansion with those of freshly isolated populations. T cells expressing an anti-B-cell-maturation-antigen (BCMA) chimeric antigen receptor (CAR) were expanded in vitro for 10 days and then cryopreserved...
June 14, 2018: Cryobiology
https://www.readbyqxmd.com/read/29907688/correction-tem8-antxr1-specific-car-t-cells-as-a-targeted-therapy-for-triple-negative-breast-cancer
#18
(no author information available yet)
No abstract text is available yet for this article.
June 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29907589/il1-blockade-may-ameliorate-cytokine-release-syndrome
#19
(no author information available yet)
Targeting IL1 attenuates cytokine release syndrome (CRS) without affecting CAR T-cell antitumor activity.
June 15, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29907163/cytokine-release-syndrome
#20
REVIEW
Alexander Shimabukuro-Vornhagen, Philipp Gödel, Marion Subklewe, Hans Joachim Stemmler, Hans Anton Schlößer, Max Schlaak, Matthias Kochanek, Boris Böll, Michael S von Bergwelt-Baildon
During the last decade the field of cancer immunotherapy has witnessed impressive progress. Highly effective immunotherapies such as immune checkpoint inhibition, and T-cell engaging therapies like bispecific T-cell engaging (BiTE) single-chain antibody constructs and chimeric antigen receptor (CAR) T cells have shown remarkable efficacy in clinical trials and some of these agents have already received regulatory approval. However, along with growing experience in the clinical application of these potent immunotherapeutic agents comes the increasing awareness of their inherent and potentially fatal adverse effects, most notably the cytokine release syndrome (CRS)...
June 15, 2018: Journal for Immunotherapy of Cancer
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