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T cell adopted therapy

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https://www.readbyqxmd.com/read/28921946/biomimetic-magnetosomes-as-versatile-artificial-antigen-presenting-cells-to-potentiate-t-cell-based-anticancer-therapy
#1
Qianmei Zhang, Wei Wei, Peiling 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 novel 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 18, 2017: ACS Nano
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28860806/enhancement-of-antitumor-activity-by-using-a-fully-human-gene-encoding-a-single-chain-fragmented-antibody-specific-for-carcinoembryonic-antigen
#15
Hirotomo Shibaguchi, Naixiang Luo, Naoto Shirasu, Motomu Kuroki, Masahide Kuroki
Human leukocyte antigen and/or costimulatory molecules are frequently lacking in metastatic tumor cells, and thus tumor cells are able to escape from the immune system. Although lymphocytes with a chimeric antigen receptor (CAR) is a promising approach for overcoming this challenge in cancer immunotherapy, administration of modified T cells alone often demonstrates little efficacy in patients. Therefore, in order to enhance the antitumor activity of immune cells in the cancer microenvironment, we used lymphocytes expressing CAR in combination with a fusion protein of IL-2 that contained the single-chain fragmented antibody (scFv) specific for the carcinoembryonic antigen...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28858287/optimized-retroviral-transduction-of-mouse-t-cells-for-in-vivo-assessment-of-gene-function
#16
Makoto Kurachi, Junko Kurachi, Zeyu Chen, John Johnson, Omar Khan, Bertram Bengsch, Erietta Stelekati, John Attanasio, Laura M McLane, Michio Tomura, Satoshi Ueha, E John Wherry
Retroviral (RV) expression of genes of interest (GOIs) is an invaluable tool and has formed the foundation of cellular engineering for adoptive cell therapy in cancer and other diseases. However, monitoring of transduced T cells long term (weeks to months) in vivo remains challenging because of the low frequency and often poor durability of transduced T cells over time when transferred without enrichment. Traditional methods often require additional overnight in vitro culture after transduction. Moreover, in vitro-generated effector CD8(+) T cells enriched by sorting often have reduced viability, making it difficult to monitor the fate of transferred cells in vivo...
September 2017: Nature Protocols
https://www.readbyqxmd.com/read/28857616/adoptive-cell-therapy-in-multiple-myeloma
#17
S Vallet, M Pecherstorfer, K Podar
Recent breakthrough advances in Multiple Myeloma (MM) immunotherapy have been achieved with the approval of the first two monoclonal antibodies, elotuzumab and daratumumab. Adoptive cell therapy (ACT) represents yet another, maybe the most powerful modality of immunotherapy, in which allogeneic or autologous effector cells are expanded and activated ex vivo followed by their re-infusion back into patients. Infused effector cells belong to two categories: naturally occurring, non-engineered cells (donor lymphocyte infusion, myeloma infiltrating lymphocytes, deltagamma T cells) or genetically- engineered antigen-specific cells (chimeric antigen receptor T or NK cells, TCR-engineered cells)...
August 31, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28854279/transfer-of-in-vitro-expanded-na%C3%A3-ve-t-cells-after-lymphodepletion-enhances-antitumor-immunity-through-the-induction-of-polyclonal-antitumor-effector-t-cells
#18
Tomohiro Tanaka, Satoshi Watanabe, Miho Takahashi, Ko Sato, Yu Saida, Junko Baba, Masashi Arita, Miyuki Sato, Aya Ohtsubo, Satoshi Shoji, Koichiro Nozaki, Kosuke Ichikawa, Rie Kondo, Nobumasa Aoki, Yasuyoshi Ohshima, Takuro Sakagami, Tetsuya Abe, Hiroshi Moro, Toshiyuki Koya, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Toshiaki Kikuchi
The adoptive transfer of effector T cells combined with lymphodepletion has demonstrated promising antitumor effects in mice and humans, although the availability of tumor-specific T cells is limited. We and others have also demonstrated that the transfer of polyclonal naïve T cells induces tumor-specific effector T cells and enhances antitumor immunity after lymphodepletion. Because tumors have been demonstrated to induce immunosuppressive networks and regulate the function of T cells, obtaining a sufficient number of fully functional naïve T cells that are able to differentiate into tumor-specific effector T cells remains difficult...
2017: PloS One
https://www.readbyqxmd.com/read/28851445/chimeric-antigen-receptors-for-adoptive-t-cell-therapy-in-acute-myeloid-leukemia
#19
REVIEW
Mingxue Fan, Minghao Li, Lipeng Gao, Sicong Geng, Jing Wang, Yiting Wang, Zhiqiang Yan, Lei Yu
Currently, conventional therapies for acute myeloid leukemia (AML) have high failure and relapse rates. Thus, developing new strategies is crucial for improving the treatment of AML. With the clinical success of anti-CD19 chimeric antigen receptor (CAR) T cell therapies against B-lineage malignancies, many studies have attempted to translate the success of CAR T cell therapy to other malignancies, including AML. This review summarizes the current advances in CAR T cell therapy against AML, including preclinical studies and clinical trials, and discusses the potential AML-associated surface markers that could be used for further CAR technology...
August 29, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28840981/bioengineering-solutions-for-manufacturing-challenges-in-car-t-cells
#20
REVIEW
Nicole J Piscopo, Katherine P Mueller, Amritava Das, Peiman Hematti, William L Murphy, Sean P Palecek, Christian M Capitini, Krishanu Saha
The next generation of therapeutic products to be approved for the clinic is anticipated to be cell therapies, termed "living drugs" for their capacity to dynamically and temporally respond to changes during their production ex vivo and after their administration in vivo. Genetically engineered chimeric antigen receptor (CAR) T cells have rapidly developed into powerful tools to harness the power of immune system manipulation against cancer. Regulatory agencies are beginning to approve CAR T cell therapies due to their striking efficacy in treating some hematological malignancies...
August 25, 2017: Biotechnology Journal
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