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Adoptive immunotherapy

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https://www.readbyqxmd.com/read/28651074/chimeric-antigen-receptor-engineered-natural-killer-and-natural-killer-t-cells-for-cancer-immunotherapy
#1
REVIEW
Dominique Bollino, Tonya J Webb
Natural killer (NK) cells of the innate immune system and NK T (NKT) cells, which have roles in both the innate and adaptive responses, are unique lymphocyte subsets that have similarities in their functions and phenotypes. Both cell types can rapidly respond to the presence of tumor cells and participate in immune surveillance and antitumor immune responses. This has incited interest in the development of novel cancer therapeutics based on NK and NKT cell manipulation. Chimeric antigen receptors (CARs), generated through the fusion of an antigen-binding region of a monoclonal antibody or other ligand to intracellular signaling domains, can enhance lymphocyte targeting and activation toward diverse malignancies...
June 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28649577/in%C3%A2-vivo-murine-matured-human-cd3-cells-as-a-preclinical-model-for-t-cell-based-immunotherapies
#2
Kevin G Haworth, Christina Ironside, Zachary K Norgaard, Willimark M Obenza, Jennifer E Adair, Hans-Peter Kiem
Adoptive cellular immunotherapy is a promising and powerful method for the treatment of a broad range of malignant and infectious diseases. Although the concept of cellular immunotherapy was originally proposed in the 1990s, it has not seen successful clinical application until recent years. Despite significant progress in creating engineered receptors against both malignant and viral epitopes, no efficient preclinical animal models exist for rapidly testing and directly comparing these engineered receptors...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28644973/il-18-il-15-il-12-synergy-induces-elevated-and-prolonged-ifn-%C3%AE-production-by-ex-vivo-expanded-nk-cells-which-is-not-due-to-enhanced-stat4-activation
#3
Evan Lusty, Sophie M Poznanski, Karen Kwofie, Talveer S Mandur, Dean A Lee, Carl D Richards, Ali A Ashkar
The synergistic effect of IL-18/IL-15/IL-12 stimulation potently activates NK cells, inducing high levels of IFN-γ production. As a result of this potent stimulatory effect, NK cell pre-activation with IL-18/IL-15/IL-12 is being developed as a cancer immunotherapy. Ex vivo expansion of NK cells enables the efficient generation of large numbers of NK cells for wide-scale and repeated therapeutic use, and is thus an important source of NK cells for clinical application. However, the effects of IL-18/IL-15/IL-12 stimulation on ex vivo expanded NK cells have not yet been assessed...
June 20, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28641664/-research-progress-of-cell-immunotherapy-in-treatment-of-hematological-malignancies-review
#4
Wei Zhang, Hong-Mei Jing, Ji-Jun Wang, Xiao-Yan Ke
Cell immunotherapy, as an important mean of tumor therapy, infuses a large number of immune effector cells amplified in vitro to the patients, resulting in the anti-tumor effect. There have been a series techniques of cell immunotherapy, including T lymphocyte therapy, dendritic cell-based immune cell therapy, natural killer cell therapy, gamma delta T cell therapy and so on. The preparation and culture conditions, anti-tumor mechanism, target cells etc of these immune cells are not the same, the each with its advantages and disadvantages...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28638729/cellular-immunotherapies-for-cancer
#5
REVIEW
Pedro Berraondo, Sara Labiano, Luna Minute, Iñaki Etxeberria, Marcos Vasquez, Alvaro Sanchez-Arraez, Alvaro Teijeira, Ignacio Melero
Lessons learned over decades on the use of gene and cell therapies have found clinical applicability in the field of cancer immunotherapy. On December 16(th), 2016 a symposium was held in Pamplona (Spain) to analyze and discuss the critical points for the clinical success of adoptive cell transfer strategies in cancer immunotherapy. Cellular immunotherapy is being currently exploited for the development of new cancer vaccines using ex vivo manipulated dendritic cells or to enhance the number of effector cells, transferring reinvigorated NK cells or T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28637663/ny-eso-1-tcr-single-edited-central-memory-and-memory-stem-t-cells-to-treat-multiple-myeloma-without-inducing-gvhd
#6
Sara Mastaglio, Pietro Genovese, Zulma Magnani, Eliana Ruggiero, Elisa Landoni, Barbara Camisa, Giulia Schiroli, Elena Provasi, Angelo Lombardo, Andreas Reik, Nicoletta Cieri, Martina Rocchi, Giacomo Oliveira, Giulia Escobar, Monica Casucci, Bernhard Gentner, Antonello Spinelli, Anna Mondino, Attilio Bondanza, Luca Vago, Maurilio Ponzoni, Fabio Ciceri, Michael C Holmes, Luigi Naldini, Chiara Bonini
Transfer of T cell receptors (TCR) specific for tumor-associated antigens is a promising approach for cancer immunotherapy. We developed the TCR gene editing technology, that is based on the knockout of the endogenous TCR α and β genes, followed by the introduction of tumor-specific TCR genes, and that proved safer and more effective than conventional TCR gene transfer. While successful, complete editing requires extensive cell manipulation and four transduction procedures. Here we propose a novel and clinically feasible 'single TCR editing' (SE) approach, based on the disruption of the endogenous TCR α chain only, followed by the transfer of genes encoding for a tumor specific TCR...
June 21, 2017: Blood
https://www.readbyqxmd.com/read/28636555/overcoming-resistance-to-targeted-therapy-with-immunotherapy-and-combination-therapy-for-metastatic-melanoma
#7
REVIEW
Hilary R Keller, Xin Zhang, Li Li, Helmut Schaider, James W Wells
Resistance to targeted therapy is an ongoing problem for the successful treatment of Stage IV metastatic melanoma. For many patients, the use of targeted therapies, such as BRAF kinase inhibitors, were initially promising yet resistance inevitably occurred. Even after combining BRAF kinase inhibitors with MEK pathway inhibitors to offset re-activation of the MAP kinase pathway, resistance is still documented. Similarly, outcomes with immune checkpoint inhibitors as monotherapy were optimistic for some patients without relapse or progression, yet the majority of patients undergoing monotherapy have progressive disease...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634816/critical-biological-parameters-modulate-affinity-as-a-determinant-of-function-in-t-cell-receptor-gene-modified-t-cells
#8
Timothy T Spear, Yuan Wang, Kendra C Foley, David C Murray, Gina M Scurti, Patricia E Simms, Elizabeth Garrett-Mayer, Lance M Hellman, Brian M Baker, Michael I Nishimura
T-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity...
June 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28633756/immunotherapy-the-wave-of-the-future-in-bladder-cancer
#9
Daniel P Petrylak
Urothelial cell carcinoma (UC) is one of the most common cancers and one of the most deadly. Metastatic UC is particularly hard to treat, because it is typically diagnosed when patients are elderly and have medical comorbidities. Many patients with metastatic UC are unable to receive cisplatin-based chemotherapy, due to older age at diagnosis and comorbidities, and even when platinum chemotherapy can be administered, it has limited success in prolonging survival. Recently, improved understanding of molecular targets and immunologic characteristics of urothelial tumor cells has resulted in new therapeutic approaches that may help optimize first- and second-line therapy...
June 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28633036/recent-advances-in-understanding-multiple-myeloma
#10
REVIEW
Parameswaran Hari
There have been major recent advancements in the understanding and management of multiple myeloma which in turn has led to unprecedented survival outcomes for patients. Diagnostic and response criteria have been recently revised. Our understanding of clonal progression, evolution, and clonal tides will inform therapeutic choices and appropriate treatment for patients. Response rates to initial induction with modern triplet therapies containing proteasome inhibitors and immunomodulators have made this approach the global standard for initial treatment...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28629761/cytokines-for-the-induction-of-antitumor-effectors-the-paradigm-of-cytokine-induced-killer-cik-cells
#11
Elisa Cappuzzello, Roberta Sommaggio, Paola Zanovello, Antonio Rosato
Cytokine-Induced killer (CIK) cells are raising growing interest in cellular antitumor therapy, as they can be easily expanded with a straightforward and inexpensive protocol, and are safe requiring only GMP-grade cytokines to obtain very high amounts of cytotoxic cells. CIK cells do not need antigen-specific stimuli to be activated and proliferate, as they recognize and destroy tumor cells in an HLA-independent fashion through the engagement of NKG2D. In several preclinical studies and clinical trials, CIK cells showed a reduced alloreactivity compared to conventional T cells, even when challenged across HLA-barriers; only in a few patients, a mild GVHD occurred after treatment with allogeneic CIK cells...
June 3, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28628043/immunotherapy-for-transplantation-associated-viral-infections
#12
Claire Roddie, Karl S Peggs
Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections following allogeneic hematopoietic stem cell transplantation (HSCT) are a major cause of morbidity and mortality. Early clinical trials demonstrate that adoptive transfer of donor-derived virus-specific T cells to restore virus-specific immunity is an effective strategy to control CMV and EBV infection after HSCT, conferring protection in 70%-90% of patients. The field has evolved rapidly to develop solutions to some of the manufacturing challenges identified in early clinical studies, such as prolonged in vitro culture, optimization of the purity of the virus-specific T cell product, the potential limitations of targeting a single viral antigen, and how to manage the patient with a virus-naive donor...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28625829/combinatorial-immunotherapy-and-nanoparticle-mediated-hyperthermia
#13
Austin J Moy, James W Tunnell
Immune checkpoint therapy has become the first widely adopted immunotherapy for patients with late stage malignant melanoma, with potential for a wide range of cancers. While some patients can experience long term disease remission, this is limited only to a subset of patients and tumor types. The path forward to expand this therapy to more patients and tumor types is currently thought to be combinatorial treatments, the combination of immunotherapy with other treatments. In this review, the combinatorial approach of immune checkpoint therapy combined with nanoparticle-assisted localized hyperthermia is discussed, starting with an overview of the different nanoparticle hyperthermia approaches in development, an overview of the state of immune checkpoint therapy, recent reports of immune checkpoint therapy and nanoparticle-assisted hyperthermia in a combinatorial approach, and finally a discussion of future research topics and areas to be explored in this new combinatorial approach to cancer treatment...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28625827/cells-as-advanced-therapeutics-state-of-the-art-challenges-and-opportunities-in-large-scale-biomanufacturing-of-high-quality-cells-for-adoptive-immunotherapies
#14
Nate J Dwarshuis, Kirsten Parratt, Adriana Santiago-Miranda, Krishnendu Roy
Therapeutic cells hold tremendous promise in treating currently incurable, chronic diseases since they perform multiple, integrated, complex functions in vivo compared to traditional small-molecule drugs or biologics. However, they also pose significant challenges as therapeutic products because (a) their complex mechanisms of actions are difficult to understand and (b) low-cost bioprocesses for large-scale, reproducible manufacturing of cells have yet to be developed. Immunotherapies using T cells and dendritic cells (DCs) have already shown great promise in treating several types of cancers, and human mesenchymal stromal cells (hMSCs) are now extensively being evaluated in clinical trials as immune-modulatory cells...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28623908/programmed-death-ligand-1-pd-l1-is-expressed-in-a-significant-number-of-the-uterine-cervical-carcinomas
#15
Opal L Reddy, Peter I Shintaku, Neda A Moatamed
BACKGROUND: The programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) immune regulatory axis has emerged as a promising new target for cancer therapeutics, with lasting responses seen in the treatment of metastatic renal and lung carcinomas, as well as melanomas. As tumor surface expression of PD-L1 has been found to correlate with objective responses to anti-PD-L1 immunotherapies, we investigated the expression of PD-L1 in human cervical tumors and provide an adopted scoring system for the systematic evaluation of PD-L1 staining...
June 17, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28620386/the-rise-of-allogeneic-natural-killer-cells-as-a-platform-for-cancer-immunotherapy-recent-innovations-and-future-developments
#16
REVIEW
John P Veluchamy, Nina Kok, Hans J van der Vliet, Henk M W Verheul, Tanja D de Gruijl, Jan Spanholtz
Natural killer (NK) cells are critical immune effector cells in the fight against cancer. As NK cells in cancer patients are highly dysfunctional and reduced in number, adoptive transfer of large numbers of cytolytic NK cells and their potential to induce relevant antitumor responses are widely explored in cancer immunotherapy. Early studies from autologous NK cells have failed to demonstrate significant clinical benefit. In this review, the clinical benefits of adoptively transferred allogeneic NK cells in a transplant and non-transplant setting are compared and discussed in the context of relevant NK cell platforms that are being developed and optimized by various biotech industries with a special focus on augmenting NK cell functions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28617989/1-25-dihydroxyvitamin-d3-induced-dendritic-cells-suppress-experimental-autoimmune-encephalomyelitis-by-increasing-proportions-of-the-regulatory-lymphocytes-and-reducing-th1-th17-cells
#17
Zhongxiang Xie, Jingtao Chen, Chao Zheng, Jing Wu, Yun Cheng, Shan Zhu, Chenhong Lin, Qingqing Cao, Jie Zhu, Tao Jin
Dendritic cells (DCs), a bridge of innate and adaptive immune responses, play a key role in the development of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Administration of tolerogenic DCs has been used as an immunotherapy in the autoimmune diseases. Deficiency of vitamin D is an environmental risk factor of MS. In this study, we induced tolerogenic DCs by 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) and adoptive transferred the tolerogenic DCs (VD3-DCs) into EAE mice...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28615225/enhanced-therapeutic-efficacy-and-memory-of-tumor-specific-cd8-t-cells-by-ex-vivo-pi3k-%C3%AE-inhibition
#18
Rasha Abu-Eid, Shamim Ahmad, Yuan Lin, Mason Webb, Zuzana Berrong, Rajeev K Shrimali, Takumi Kumai, Sudha Ananth, Paulo C Rodriguez, Esteban Celis, John E Janik, Mikayel Mkrtichyan, Samir N Khleif
Inhibition of specific Akt isoforms in CD8+ T cells promotes favored differentiation into memory versus effector cells, the former of which are superior in mediating anti-tumor immunity. In this study, we investigated the role of upstream PI3K isoforms in CD8+ T cell differentiation and assessed the potential use of PI3K isoform-specific inhibitors to favorably condition CD8+ T cells for adoptive cell therapy. The phenotype and proliferative ability of tumor antigen specific CD8+ T cells was assessed in the presence of PI3K-α, -β, or -δ inhibitors...
June 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28614795/a-3d-microfluidic-model-for-preclinical-evaluation-of-tcr-engineered-t-cells-against-solid-tumors
#19
Andrea Pavesi, Anthony T Tan, Sarene Koh, Adeline Chia, Marta Colombo, Emanuele Antonecchia, Carlo Miccolis, Erica Ceccarello, Giulia Adriani, Manuela T Raimondi, Roger D Kamm, Antonio Bertoletti
The tumor microenvironment imposes physical and functional constraints on the antitumor efficacy of adoptive T cell immunotherapy. Preclinical testing of different T cell preparations can help in the selection of efficient immune therapies, but in vivo models are expensive and cumbersome to develop, while classical in vitro 2D models cannot recapitulate the spatiotemporal dynamics experienced by T cells targeting cancer. Here, we describe an easily customizable 3D model, in which the tumor microenvironment conditions are modulated and the functionality of different T cell preparations is tested...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28604557/antigen-presentation-by-individually-transferred-hla-class-i-genes-in-hla-a-hla-b-hla-c-null-human-cell-line-generated-using-the-multiplex-crispr-cas9-system
#20
Cheol-Hwa Hong, Hyun-Jung Sohn, Hyun-Joo Lee, Hyun-Il Cho, Tai-Gyu Kim
Human leukocyte antigens (HLAs) are essential immune molecules that affect transplantation and adoptive immunotherapy. When hematopoietic stem cells or organs are transplanted with HLA-mismatched recipients, graft-versus-host disease or graft rejection can be induced by allogeneic immune responses. The function of each HLA allele has been studied using HLA-deficient cells generated from mutant cell lines or by RNA interference, zinc finger nuclease, and the CRISPR/Cas9 system. To improve HLA gene editing, we attempted to generate an HLA class I null cell line using the multiplex CRISPR/Cas9 system by targeting exons 2 and 3 of HLA-A, HLA-B, and HLA-C genes simultaneously...
July 2017: Journal of Immunotherapy
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