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Adoptive T-Cell Therapy

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https://www.readbyqxmd.com/read/28935774/immunotherapy-a-new-and-old-approach-to-treatment-of-soft-tissue-and-bone-sarcomas
#1
REVIEW
Michael J Nathenson, Anthony P Conley, Edward Sausville
Soft tissue and bone sarcomas are a rare and heterogeneous form of cancer. With standard of care treatment options including surgery, radiation, and chemotherapy, the long-term survival is still low for high-risk soft tissue sarcoma patients. New treatment strategies are needed. Immunotherapy offers a new potential treatment paradigm with great promise. Immunotherapy of soft tissue sarcomas dates back to Dr. Coley's first use of toxins in the late 1800s. A variety of strategies of immunotherapy have been tried in soft tissue and bone sarcomas, including various vaccines and cytokines, with limited success...
September 21, 2017: Oncologist
https://www.readbyqxmd.com/read/28932632/local-endothelial-complement-activation-reverses-endothelial-quiescence-enabling-t-cell-homing-and-tumor-control-during-t-cell-immunotherapy
#2
Andrea Facciabene, Francesco De Sanctis, Stefano Pierini, Edimara S Reis, Klara Balint, John Facciponte, Jens Rueter, Masahiro Kagabu, Paola Magotti, Evripidis Lanitis, Robert A DeAngelis, Ronald J Buckanovich, Wenchao C Song, John D Lambris, George Coukos
Cancer immunotherapy relies upon the ability of T cells to infiltrate tumors. The endothelium constitutes a barrier between the tumor and effector T cells, and the ability to manipulate local vascular permeability could be translated into effective immunotherapy. Here, we show that in the context of adoptive T cell therapy, antitumor T cells, delivered at high enough doses, can overcome the endothelial barrier and infiltrate tumors, a process that requires local production of C3, complement activation on tumor endothelium and release of C5a...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28927824/cellular-therapy-for-multiple-pathogen-infections-after-hematopoietic-stem-cell-transplant
#3
REVIEW
Gaurav Sutrave, Emily Blyth, David J Gottlieb
Hematopoietic stem cell transplantation (HSCT) represents the only crative treatment option for many hematological conditions but results in a profound T-cell deficiency in the post-HSCT period. Infections account for a significant proportion of non-relapse morbidity and mortality, and infections with multiple organisms either simultaneously or at different times after transplant are common. Adoptive cellular therapy (ACT) with prophylactic or therapeutic infusion of donor derived or third-party, pathogen-specific T-cells represents a novel methodology to rapidly reconstitute T-cell mediated immunity in this context...
September 15, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28927823/t-cell-therapies-for-human-polyomavirus-diseases
#4
REVIEW
Sarah I Davies, Pawel Muranski
Rapid restoration of virus-specific T immunity via adoptive transfer of ex vivo generated T cells has been proven as a powerful therapy for patients with advanced cancers and refractory viral infections such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV). BK virus (BKV), John Cunningham virus (JCV), and Merkel cell carcinoma virus (MCV) are the members of the rapidly growing human polyomavirus (hPyV) family that commonly infects most healthy humans. These viruses have a clearly established potential for causing severe end-organ damage or malignant transformation, especially in individuals with weakened immunity who are unable to mount or regain endogenous T-cell responses as a result of underlying leukemia or iatrogenic immunosuppression in autoimmunity, bone marrow and solid organ transplant settings...
September 15, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28925994/chimeric-antigen-receptor-t-cell-therapy-assessment-and-management-of-toxicities
#5
REVIEW
Sattva S Neelapu, Sudhakar Tummala, Partow Kebriaei, William Wierda, Cristina Gutierrez, Frederick L Locke, Krishna V Komanduri, Yi Lin, Nitin Jain, Naval Daver, Jason Westin, Alison M Gulbis, Monica E Loghin, John F de Groot, Sherry Adkins, Suzanne E Davis, Katayoun Rezvani, Patrick Hwu, Elizabeth J Shpall
Immunotherapy using T cells genetically engineered to express a chimeric antigen receptor (CAR) is rapidly emerging as a promising new treatment for haematological and non-haematological malignancies. CAR-T-cell therapy can induce rapid and durable clinical responses, but is associated with unique acute toxicities, which can be severe or even fatal. Cytokine-release syndrome (CRS), the most commonly observed toxicity, can range in severity from low-grade constitutional symptoms to a high-grade syndrome associated with life-threatening multiorgan dysfunction; rarely, severe CRS can evolve into fulminant haemophagocytic lymphohistiocytosis (HLH)...
September 19, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28923424/depletion-of-regulatory-t-cells-by-anti-icos-antibody-enhances-anti-tumor-immunity-of-tumor-cell-vaccine-in-prostate-cancer
#6
Lijun Mo, Qianmei Chen, Xinji Zhang, Xiaojun Shi, Lili Wei, Dianpeng Zheng, Hongwei Li, Jimin Gao, Jinlong Li, Zhiming Hu
ICOS(+)Treg cells exert important immunosuppressive effects in tumor immunity. We adopt a combination approach of ICOS(+)Treg cells depletion with tumor cell vaccine to evaluate anti-tumor immunity in mouse prostate cancer model. Streptavidin (SA)-mGM-CSF surface-modified RM-1 cells were prepared as the vaccine and the mouse subcutaneous prostate tumor model was used to evaluate the immunity. Tumor growth, flow cytometry, immunohistochemistry, immunofluorescence and enzyme linked immunosorbent assay (ELISA) were performed to evaluate the therapeutic effects...
September 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28921946/biomimetic-magnetosomes-as-versatile-artificial-antigen-presenting-cells-to-potentiate-t-cell-based-anticancer-therapy
#7
Qianmei Zhang, Wei Wei, Peilin Wang, Liping Zuo, Feng Li, Jin Xu, Xiaobo Xi, Xiaoyong Gao, Guanghui Ma, Hai-Yan Xie
Adoptive T-cell transfer for cancer therapy relies on both effective ex vivo T-cell expansion and in vivo targeting performance. One promising but challenging method for accomplishing this purpose is to construct multifunctional artificial antigen-presenting cells (aAPCs). We herein developed biomimetic magnetosomes as versatile aAPCs, wherein magnetic nanoclusters were coated with azide-engineered leucocyte membranes and then decorated with T-cell stimuli through copper-free click chemistry. These nano aAPCs not only exhibited high performance for antigen-specific cytotoxic T-cell (CTL) expansion and stimulation but also visually and effectively guided reinfused CTLs to tumor tissues through magnetic resonance imaging and magnetic control...
September 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#8
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28916658/t-cells-deficient-in-diacylglycerol-kinase-%C3%AE-are-resistant-to-pd-1-inhibition-and-help-create-persistent-host-immunity-to-leukemia
#9
Weiqing Jing, Jill Alane Gershan, Sandra Holzhauer, James Weber, Katie Palen, Laura McOlash, Kirthi Pulakanti, Erin Wesley, Sridhar Rao, Bryon D Johnson, Matthew J Riese
Efforts to improve the efficacy of adoptive T cell therapies and immune checkpoint therapies in myelogenous leukemia are desired. In this study, we evaluated the anti-leukemia activity of adoptively transferred polyclonal cancer antigen-reactive T cells deficient in the regulator diacylglycerol kinase-zeta (DGKζ) with or without PD-1/PD-L1 blockade. In the C1498 mouse model of myeloid leukemia, we showed that leukemia was eradicated more effectively in DGKζ-deficient (DGKζ-/-) mice than wild-type mice. T cells transferred from DGKζ-deficient mice to wild-type tumor-bearing recipients conferred this benefit...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28912399/-adoptive-cell-therapy-with-immune-checkpoint-blockade
#10
Atsushi Aruga
Cancer immunotherapy are taking a leading role of cancer therapy due to the development of the immune checkpoint blockade. To date, however, only about 20% of patients have clinical responses and the cancer-specific T cells in cancer site are required to obtain beneficial effects. There has been an innovative development in the field of adoptive cell therapy, especially receptor gene-modified T cells in recent years. The effector cells mostly express PD-1, therefore the cytotoxic reactivity of the effector cells are inhibited by PD-L1...
September 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28910387/epstein-barr-virus-latent-membrane-protein-1-enhances-dendritic-cell-therapy-lymph-node-migration-activation-and-il-12-secretion
#11
James M Termini, Sachin Gupta, Francesca N Raffa, Elizabeth Guirado, Margaret A Fischl, Liguo Niu, Saravana Kanagavelu, Geoffrey W Stone
Dendritic cells (DC) are a promising cell type for cancer vaccines due to their high immunostimulatory capacity. However, improper maturation of DC prior to treatment may account for the limited efficacy of DC vaccine clinical trials. Latent Membrane Protein-1 (LMP1) of Epstein-Barr virus was examined for its ability to mature and activate DC as a gene-based molecular adjuvant for DC vaccines. DC were transduced with an adenovirus 5 vector (Ad5) expressing LMP1 under the control of a Tet-inducible promoter...
2017: PloS One
https://www.readbyqxmd.com/read/28877635/two-is-better-than-one-advances-in-pathogen-boosted-immunotherapy-and-adoptive-t-cell-therapy
#12
Gang Xin, David M Schauder, Ryan Zander, Weiguo Cui
The recent tremendous successes in clinical trials take cancer immunotherapy into a new era and have attracted major attention from both academia and industry. Among the variety of immunotherapy strategies developed to boost patients' own immune systems to fight against malignant cells, the pathogen-based and adoptive cell transfer therapies have shown the most promise for treating multiple types of cancer. Pathogen-based therapies could either break the immune tolerance to enhance the effectiveness of cancer vaccines or directly infect and kill cancer cells...
September 2017: Immunotherapy
https://www.readbyqxmd.com/read/28877629/application-of-chimeric-antigen-receptor-engineered-t-cells-in-ovarian-cancer-therapy
#13
Minghui Zhang, Dr Bin Zhang, Huirong Shi
Due to the critical role of T cells in the immune surveillance of ovarian cancer, adoptive T-cell therapies are receiving increased attention as an immunotherapeutic approach for ovarian cancer. Chimeric antigen receptors (CARs), constructed by incorporating the single-chain Fv fragment to a T-cell signaling domain such as CD3 ζ or Fc receptor γ chain, endow T cell with nonmajor histocompatibility complex-restricted specificity. Dual specificity, trans-signaling CARs and affinity-tuned single-chain Fv fragment have broadened the applicability of CAR-engineered T-cell therapy and may be considered preferential to T cell receptor T-cell therapy in clinical care...
September 2017: Immunotherapy
https://www.readbyqxmd.com/read/28877078/advances-in-immunotherapy-in-multiple-myeloma
#14
Leora Boussi, Ruben Niesvizky
PURPOSE OF REVIEW: Here, we explore the significant progress made in the treatment of multiple myeloma, focusing on immunotherapy and the promise it has offered to patients suffering from advanced disease. RECENT FINDINGS: Multiple myeloma, a B-cell malignancy, is characterized by unregulated plasma cell growth in the bone marrow as well as strong immunosuppression in the tumor microenvironment. mAbs targeting tumor antigens overcome this, increasing T-cell activation, multiple myeloma cell death, and depth of response...
September 4, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28876947/integrin-assisted-t-cell-activation-on-nanostructured-hydrogels
#15
Judith Guasch, Christine A Muth, Jennifer Diemer, Hossein Riahinezhad, Joachim P Spatz
Adoptive cell therapy (ACT) has shown very promising results as treatment for cancer in a few clinical trials, such as the complete remissions of otherwise terminal leukemia patients. Nevertheless, the introduction of ACT into clinics requires overcoming not only medical but also technical challenges, such as the ex vivo expansion of large amounts of specific T-cells. Nanostructured surfaces represent a novel T-cell stimulation technique that enables us to fine-tune the density and orientation of activating molecules presented to the cells...
September 6, 2017: Nano Letters
https://www.readbyqxmd.com/read/28874817/armored-car-t-cells-enhance-antitumor-efficacy-and-overcome-the-tumor-microenvironment
#16
Oladapo O Yeku, Terence J Purdon, Mythili Koneru, David Spriggs, Renier J Brentjens
Chimeric antigen receptor (CAR) T cell therapy has shown limited efficacy for the management of solid tumor malignancies. In ovarian cancer, this is in part due to an immunosuppressive cytokine and cellular tumor microenvironment which suppresses adoptively transferred T cells. We engineered an armored CAR T cell capable of constitutive secretion of IL-12, and delineate the mechanisms via which these CAR T cells overcome a hostile tumor microenvironment. In this report, we demonstrate enhanced proliferation, decreased apoptosis and increased cytotoxicity in the presence of immunosuppressive ascites...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28871274/paired-expression-analysis-of-tumor-cell-surface-antigens
#17
Rimas J Orentas, Sivasish Sindiri, Christine Duris, Xinyu Wen, Jianbin He, Jun S Wei, Jason Jarzembowski, Javed Khan
Adoptive immunotherapy with antibody-based therapy or with T cells transduced to express chimeric antigen receptors (CARs) is useful to the extent that the cell surface membrane protein being targeted is not expressed on normal tissues. The most successful CAR-based (anti-CD19) or antibody-based therapy (anti-CD20) in hematologic malignancies has the side effect of eliminating the normal B cell compartment. Targeting solid tumors may not provide a similar expendable marker. Beyond antibody to Her2/NEU and EGFR, very few antibody-based and no CAR-based therapies have seen broad clinical application for solid tumors...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28868758/programmed-cell-death-ligand-1-pd-l1-expression-is-not-a-predominant-feature-in-ewing-sarcomas
#18
Christian Spurny, Sareetha Kailayangiri, Silke Jamitzky, Bianca Altvater, Eva Wardelmann, Uta Dirksen, Jendrik Hardes, Wolfgang Hartmann, Claudia Rossig
BACKGROUND: Programmed cell death 1 (PD-1) receptor engagement on T cells by its ligand programmed cell death ligand 1 (PD-L1) is a key mechanism of immune escape, and antibody blockade of the interaction has emerged as an effective immunotherapeutic strategy in some cancers. The role and relevance of the PD-1 checkpoint in Ewing sarcoma (EwS) is not yet understood. PROCEDURE: Here, we investigated expression of PD-L1 and PD-1 in EwS by immunohistochemistry analysis of pretherapeutic tumor biopsies and in tumor xenografts following treatment with human T cells engineered to express a chimeric antigen receptor (CAR) against the tumor-associated antigen GD2 ...
September 4, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28867165/antitumor-antibodies-can-drive-therapeutic-t-cell-responses
#19
REVIEW
K Dane Wittrup
The classical view of therapeutic monoclonal antibodies (mAbs) against tumor-associated antigens (TAAs) is that their mechanism of action is dominated by signal blocking or the cytotoxicity of Fc-driven innate immune effector functions. We review here a mounting body of evidence that anti-TAA mAbs are capable of profoundly synergizing with T cell-directed immunotherapies such as checkpoint blockade and adoptive cell therapy. Two key components account for this synergy: (i) a self-vaccinal effect mediated by dendritic cells (DCs); and (ii) an inflammatory repolarization of the tumor microenvironment...
September 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28862644/chimeric-antigen-receptor-car-t-cell-therapy-for-malignant-pleural-mesothelioma-mpm
#20
REVIEW
Astero Klampatsa, Andrew R Haas, Edmund K Moon, Steven M Albelda
Cancer immunotherapy has now become a recognized approach to treating cancers. In addition to checkpoint blockade, adoptive T cell transfer (ACT) using chimeric antigen receptors (CARs) has shown impressive clinical outcomes in leukemias and is now being explored in solid tumors. CARs are engineered receptors, stably or transiently transduced into T cells, that aim to enhance T cell effector function by recognizing and binding to a specific tumor-associated antigen. In this review, we provide a summary of CAR T cell preclinical studies and clinical trials for malignant pleural mesothelioma (MPM), a rare, locally invasive pleural cancer with poor prognosis...
September 1, 2017: Cancers
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