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Adoptive immunotherapy

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https://www.readbyqxmd.com/read/28927823/t-cell-therapies-for-human-polyomavirus-diseases
#1
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
#2
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/28923358/targets-for-immunotherapy-of-liver-cancer
#3
REVIEW
Tim F Greten, Bruno Sangro
Drug development in HCC has been characterized in the past by many failures. Despite good rationales and promising phase II data, many phase III trials failed. Immunotherapy represents an alternate treatment approach and has been successful in many different types of cancer. Being an inflammation induced cancer HCC represents a very interesting target for immune based approaches and indeed early results from clinical trials testing immune checkpoint inhibitors are not only promising but have already led to evaluation of such in a phase III setting...
September 15, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28921946/biomimetic-magnetosomes-as-versatile-artificial-antigen-presenting-cells-to-potentiate-t-cell-based-anticancer-therapy
#4
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
#5
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/28919991/umbilical-cord-blood-cd34-progenitor-derived-nk-cells-efficiently-kill-ovarian-cancer-spheroids-and-intraperitoneal-tumors-in-nod-scid-il2rg-null-mice
#6
Janneke S Hoogstad-van Evert, Jeannette Cany, Dirk van den Brand, Manon Oudenampsen, Roland Brock, Ruurd Torensma, Ruud L Bekkers, Joop H Jansen, Leon F Massuger, Harry Dolstra
Adoptive transfer of allogeneic natural killer (NK) cells is an attractive therapy approach against ovarian carcinoma. Here, we evaluated the potency of highly active NK cells derived from human CD34+ haematopoietic stem and progenitor cells (HSPC) to infiltrate and mediate killing of human ovarian cancer spheroids using an in vivo-like model system and mouse xenograft model. These CD56+Perforin+ HSPC-NK cells were generated under stroma-free conditions in the presence of StemRegenin-1, IL-15, and IL-12, and exerted efficient cytolytic activity and IFNγ production toward ovarian cancer monolayer cultures...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919988/identification-of-a-hla-a-0201-restricted-immunogenic-epitope-from-the-universal-tumor-antigen-depdc1
#7
Anna Tosi, Silvia Dalla Santa, Elisa Cappuzzello, Carolina Marotta, Dawid Walerich, Giannino Del Sal, Paola Zanovello, Roberta Sommaggio, Antonio Rosato
The identification of universal tumor-specific antigens shared between multiple patients and/or multiple tumors is of great importance to overcome the practical limitations of personalized cancer immunotherapy. Recent studies support the involvement of DEPDC1 in many aspects of cancer traits, such as cell proliferation, resistance to induction of apoptosis and cell invasion, suggesting that it may play key roles in the oncogenic process. In this study, we report that DEPDC1 expression is upregulated in most types of human tumors, and closely linked to a poorer prognosis; therefore, it might be regarded as a novel universal oncoantigen potentially suitable for targeting many different cancers...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28912399/-adoptive-cell-therapy-with-immune-checkpoint-blockade
#8
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/28888619/natural-killer-cell-mediated-immunosurveillance-of-human-cancer
#9
REVIEW
Karl-Johan Malmberg, Mattias Carlsten, Andreas Björklund, Ebba Sohlberg, Yenan T Bryceson, Hans-Gustaf Ljunggren
The contribution of natural killer (NK) cells to immunosurveillance of human cancer remains debatable. Here, we discuss advances in several areas of human NK cell research, many of which support the ability of NK cells to prevent cancer development and avoid relapse following adoptive immunotherapy. We describe the molecular basis for NK cell recognition of human tumor cells and provide evidence for NK cell-mediated killing of human primary tumor cells ex vivo. Subsequently, we highlight studies demonstrating the ability of NK cells to migrate to, and reside in, the human tumor microenvironment where selection of tumor escape variants from NK cells can occur...
September 6, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28882429/natural-killer-cells-unleashed-checkpoint-receptor-blockade-and-bike-trike-utilization-in-nk-mediated-anti-tumor-immunotherapy
#10
REVIEW
Zachary B Davis, Daniel A Vallera, Jeffrey S Miller, Martin Felices
Natural killer (NK) cells have long been known to mediate anti-tumor responses without prior sensitization or recognition of specific tumor antigens. However, the tumor microenvironment can suppress NK cell function resulting in tumor escape and disease progression. Despite recent advances in cytokine therapy and NK cell adoptive transfer, tumor expression of ligands to NK - expressed checkpoint receptors can still suppress NK mediated tumor lysis. This review will explore many of the checkpoint receptors tumors utilize to manipulate the NK cell response as well as some of the current and upcoming pharmacological solutions to limit tumor suppression of NK cell function...
September 4, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28877635/two-is-better-than-one-advances-in-pathogen-boosted-immunotherapy-and-adoptive-t-cell-therapy
#11
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/28877078/advances-in-immunotherapy-in-multiple-myeloma
#12
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/28871274/paired-expression-analysis-of-tumor-cell-surface-antigens
#13
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/28867165/antitumor-antibodies-can-drive-therapeutic-t-cell-responses
#14
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/28864289/phase-1-clinical-trial-of-adoptive-immunotherapy-using-off-the-shelf-activated-natural-killer-cells-in-patients-with-refractory-and-relapsed-acute-myeloid-leukemia
#15
Michael Boyiadzis, Mounzer Agha, Robert L Redner, Alison Sehgal, Annie Im, Jing-Zhou Hou, Rafic Farah, Kathleen A Dorritie, Anastasios Raptis, Seah H Lim, Hong Wang, Natalia Lapteva, Zhuyong Mei, Lisa H Butterfield, Cliona M Rooney, Theresa L Whiteside
BACKGROUND AIMS: Activated NK cells (aNK) generated by expansion of a human interleukin-2-dependent NK cell line (NK-92) were shown to mediate strong anti-leukemia activity. This phase 1 study evaluated feasibility, safety, and activity of aNK cells adoptively transferred to patients with refractory/relapsed acute myeloid leukemia (AML). In addition, effects of these aNK cells on the patient's immune system were evaluated. METHODS: Two cell-dose levels (1 × 10(9) cells/m(2) and 3 × 10(9) cells/m(2)) were used...
August 29, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28864137/adjuvant-peptide-pulsed-dendritic-cell-vaccination-in-addition-to-t-cell-adoptive-immunotherapy-for-cytomegalovirus-infection-in-allogeneic-hematopoietic-stem-cell-transplant-hsct-recipients
#16
Chun K K Ma, Leighton Clancy, Renee Simms, Jane Burgess, Shivashni Deo, Emily Blyth, Kenneth P Micklethwaite, David J Gottlieb
Adoptive cellular immunotherapy has been shown to be effective in the management of CMV reactivation and disease. It is unknown whether adjuvant dendritic cell vaccination will provide additional benefit in prophylaxis or treatment of CMV in HSCT patients. In this study, we administered prophylactic CMV-peptide specific T cell infusions, followed by 2 doses of intradermal CMV peptide-pulsed dendritic cell (DC) vaccine to 4 HSCT patients. There were no immediate adverse events associated with T cell infusion or DC vaccinations...
August 29, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28862644/chimeric-antigen-receptor-car-t-cell-therapy-for-malignant-pleural-mesothelioma-mpm
#17
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/28861943/surface-engineering-of-red-blood-cells-as-artificial-antigen-presenting-cells-promising-for-cancer-immunotherapy
#18
Xiaoqi Sun, Xiao Han, Ligeng Xu, Min Gao, Jun Xu, Rong Yang, Zhuang Liu
The development of artificial antigen presenting cells (aAPCs) to mimic the functions of APCs such as dendritic cells (DCs) to stimulate T cells and induce antitumor immune responses has attracted substantial interests in cancer immunotherapy. In this work, a unique red blood cell (RBC)-based aAPC system is designed by engineering antigen peptide-loaded major histocompatibility complex-I and CD28 activation antibody on RBC surface, which are further tethered with interleukin-2 (IL2) as a proliferation and differentiation signal...
September 1, 2017: Small
https://www.readbyqxmd.com/read/28861770/economic-considerations-in-the-use-of-novel-targeted-therapies-for-lung-cancer-review-of-current-literature
#19
Hamzeh Albaba, Charles Lim, Natasha B Leighl
Lung cancer remains the leading cause of cancer-related death and economic burden worldwide. Despite the heavy toll of lung cancer, multiple new advances have improved patient outcomes, largely through precision medicine and targeted therapy. The associated rising economic burden however may impact the uptake of novel therapeutic agents in lung cancer, thereby limiting patient access. This article identifies and reviews economic evaluations of targeted agents in lung cancer in the era of precision medicine...
August 31, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28861087/alanine-mutagenesis-in-the-complementarity-determining-region-3-of-the-mtb-and-hiv-1-peptide-bispecific-t-cell-receptor-beta-chain-affects-ligand-recognition
#20
Chao-Ying Zhou, Rui-Ning Wang, Qian Wen, Wen-Ting He, Shi-Meng Zhang, Xia-Lin Du, Jia-Hui Yang, Li Ma
Mycobacterium tuberculosis/human immunodeficiency virus (MTB/HIV) coinfection presents a special challenge to the prevention and treatment of tuberculosis and HIV/AIDS. Adoptive transfer of high-affinity T cell receptor (TCR) gene-modified T cells against MTB and HIV antigens is a promising approach to treating MTB/HIV coinfected patients whose cellular immunity is obviously disordered. We have previously successfully identified that a bispecific TCR screened out from peripheral blood mononuclear cells of a HLA-A*0201(+) healthy individual using the complementarity determining region 3 (CDR3) spectratype analysis recognizes both MTB Ag85B199-207 and HIV-1 Env120-128 peptide...
2017: Frontiers in Immunology
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