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https://www.readbyqxmd.com/read/28530525/cost-effectiveness-of-nivolumab-ipilimumab-combination-therapy-compared-with-monotherapy-for-first-line-treatment-of-metastatic-melanoma-in-the-united-states
#1
Anna Oh, Dang M Tran, Leann C McDowell, Dor Keyvani, Jay Andrew Barcelon, Oscar Merino, Leslie Wilson
BACKGROUND: The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations for third-party payer systems, physicians, and patients. OBJECTIVE: To develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as firstline therapy in metastatic melanoma, while accounting for differential effectiveness in programmed death-ligand 1 (PD-L1) positive and negative patients...
June 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28530241/notch-mediated-conversion-of-activated-t-cells-into-stem-cell-memory-like-t-cells-for-adoptive-immunotherapy
#2
Taisuke Kondo, Rimpei Morita, Yuumi Okuzono, Hiroko Nakatsukasa, Takashi Sekiya, Shunsuke Chikuma, Takashi Shichita, Mitsuhiro Kanamori, Masato Kubo, Keiko Koga, Takahiro Miyazaki, Yoshiaki Kassai, Akihiko Yoshimura
Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8(+) TSCM cells can be generated in vitro from naive CD8(+) T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM-like cells in vitro (iTSCM cells) from activated CD4(+) and CD8(+) T cells in mice and humans by coculturing with stromal cells that express a Notch ligand...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529840/adoptive-cell-therapy-with-tregs-to-improve-transplant-outcomes-the-promise-and-the-stumbling-blocks
#3
Mohamed B Ezzelarab, Angus W Thomson
The contribution of regulatory T cells (Treg) to the induction and maintenance of tolerance is well-recognized in rodents and may contribute to long-term human organ allograft survival. The therapeutic efficacy of adoptively-transferred Treg in promoting tolerance to organ allografts is well-recognized in mouse models. Early phase 1/2 clinical studies of Treg therapy have been conducted in patients with type-1 (autoimmune) diabetes and refractory Crohn's disease, and for inhibition of graft-versus-host disease following bone marrow transplantation with proven safety...
December 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28527946/the-microbiome-and-hepatobiliary-pancreatic-cancers
#4
Kosuke Mima, Shigeki Nakagawa, Hiroshi Sawayama, Takatsugu Ishimoto, Katsunori Imai, Masaaki Iwatsuki, Daisuke Hashimoto, Yoshifumi Baba, Yo-Ichi Yamashita, Naoya Yoshida, Akira Chikamoto, Hideo Baba
The human intestinal microbiome encompasses at least 100 trillion microorganisms that can influence host immunity and disease conditions, including cancer. Hepatobiliary and pancreatic cancers have been associated with poor prognosis owing to their high level of tumor invasiveness, distant metastasis, and resistance to conventional treatment options, such as chemotherapy. Accumulating evidence from animal models suggests that specific microbes and microbial dysbiosis can potentiate hepatobiliary-pancreatic tumor development by damaging DNA, activating oncogenic signaling pathways, and producing tumor-promoting metabolites...
May 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28527911/cancer-stem-cells-at-the-forefront-of-personalized-medicine-and-immunotherapy
#5
REVIEW
Micol E Fiori, Lidia Villanova, Ruggero De Maria
Cancer stem cells (CSCs) represent the main target of the current efforts to eradicate cancer, because of their ability to promote metastatic dissemination and survive cytotoxic therapies. Here, we highlight the potential of patient-derived CSCs as an in vitro and in vivo pre-clinical model and of liquid biopsy as a diagnostic, prognostic and predictive tool. We discuss recently developed therapeutic strategies aiming at specifically targeting the cancer stem cell population, particularly focusing on the latest advances in cancer immunotherapy...
May 18, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28526624/guideline-recommendations-on-the-use-of-allergen-immunotherapy-in-house-dust-mite-allergy-time-for-a-change
#6
Moisés A Calderón, Jean Bousquet, G Walter Canonica, Lars-Olaf Cardell, Dolores Hernandez Fernandez de Rojas, Jörg Kleine-Tebbe, Pascal Demoly
Guidelines on the treatment of asthma, allergic rhinitis (AR) and allergen immunotherapy (AIT) lack recommendations for house dust mite (HDM) allergy. An expert panel reviewed current guidelines in the light of new data, to assess whether guidelines could be improved. Most guidelines and key position papers did not provide specific recommendations on treatment of allergic asthma (AA) caused by HDM allergy, although some included AIT as a treatment option for AA in general. Around half of the guidelines stated that AIT with HDM extract was an effective treatment for AR, with several indicating sublingual immunotherapy (SLIT) as an option...
May 16, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28525901/direct-inhibition-of-stat-signaling-by-platinum-drugs-contributes-to-their-anti-cancer-activity
#7
Stanleyson V Hato, Carl G Figdor, Susumu Takahashi, Anja E Pen, Altuna Halilovic, Kalijn F Bol, Angela Vasaturo, Yukie Inoue, Nienke de Haas, Dagmar Verweij, Carla M L Van Herpen, Johannes H Kaanders, Johan H J M van Krieken, Hanneke W M Van Laarhoven, Gerrit K J Hooijer, Cornelis J A Punt, Akira Asai, I Jolanda M de Vries, W Joost Lesterhuis
Platinum-based chemotherapeutics are amongst the most powerful anti-cancer drugs. Although their exact mechanism of action is not well understood, it is thought to be mediated through covalent DNA binding. We investigated the effect of platinum-based chemotherapeutics on signaling through signal transducer and activator of transcription (STAT) proteins, which are involved in many oncogenic signaling pathways. We performed in vitro experiments in various cancer cell lines, investigating the effects of platinum chemotherapeutics on STAT phosphorylation and nuclear translocation, the expression of STAT-modulating proteins and downstream signaling pathways...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523162/a-preliminary-exploration-of-the-intravoxel-incoherent-motion-applied-in-the-preoperative-evaluation-of-mediastinal-lymph-node-metastasis-of-lung-cancer
#8
Xin Ye, Shuo Chen, Yaru Tian, Bin You, Wenqian Zhang, Yan Zhao, Tao Jiang, Bin Hu, Hui Li
BACKGROUND: The aim of this study was to investigate the diagnostic value of the intravoxel incoherent motion (IVIM) for distinguishing non-metastatic from metastatic mediastinal lymph nodes in lung cancer. METHODS: IVIM-diffusion weighted imaging (DWI) exams were performed preoperatively on 66 patients with lung cancer from October 2015 to June 2016 in Beijing Chao-Yang Hospital, Capital Medical University. Fifty patients underwent enhanced chest computed tomography (CT) in our hospital, while the other 16 patients already had enhanced chest CT images when they were admitted...
April 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28523003/hpv16-e7-specific-activated-cd8-t-cells-in-e7-transgenic-skin-and-skin-grafts
#9
Seyed Davoud Jazayeri, Paula T Kuo, Graham Robert Leggatt, Ian H Frazer
Human papillomavirus (HPV) 16 E7 (E7) protein expression in skin promotes epithelial hyperproliferation and transformation to malignancy. Grafts of murine skin expressing E7 protein as a transgene in keratinocytes are not rejected from immunocompetent recipients, whereas grafts expressing ovalbumin (OVA), with or without coexpression of E7 protein, are promptly rejected, demonstrating that E7-associated non-antigen-specific local immunosuppression is not a major determinant of lack of rejection of E7 transgenic skin...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28521905/harnessing-the-properties-of-dendritic-cells-in-the-pursuit-of-immunological-tolerance
#10
REVIEW
Christopher Horton, Kumaran Shanmugarajah, Paul J Fairchild
The acquisition of self-perpetuating, immunological tolerance specific for graft alloantigens has long been described as the "holy grail" of clinical transplantation. By removing the need for life-long immunosuppression following engraftment, the adverse consequences of immunosuppressive regimens, including chronic infections and malignancy, may be avoided. Furthermore, autoimmune diseases and allergy are, by definition, driven by aberrant immunological responses to ordinarily innocuous antigens. The re-establishment of permanent tolerance towards instigating antigens may, therefore, provide a cure to these common diseases...
April 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28521640/antibody-mediated-immunotherapy-against-chronic-hepatitis-b-virus-infection
#11
Ying Gao, Tian-Ying Zhang, Quan Yuan, Ning-Shao Xia
The currently available drugs to treat hepatitis B virus (HBV) infection include interferons and nucleos(t)ide analogues, which can only induce disease remission and are inefficient for the functional cure of patients with chronic HBV infection (CHB). Since high titers of circulating hepatitis B surface antigen (HBsAg) may be essential to exhaust the host anti-HBV immune response and they cannot be significantly reduced by current drugs, new antiviral strategies aiming to suppress serum hepatitis B surface antigen (HBsAg) could help restore virus-specific immune responses and promote the eradication of the virus...
May 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28521532/new-antivirals-for-the-treatment-of-chronic-hepatitis-b
#12
Vincent Soriano, Pablo Barreiro, Laura Benitez, Jose M Peña, Carmen de Mendoza
Current treatment with oral nucleos(t)ides entecavir or tenofovir provide sustained suppression of HBV replication and clinical benefit in most chronic hepatitis B virus (HBV) infected persons. However, HBV rebound generally occurs upon drug discontinuation due to persistence of genomic HBV reservoirs as episomic cccDNA and chromosomic integrated HBV-DNA. There is renewed enthusiasm on HBV drug discovery following recent successes with antivirals for hepatitis C and immunotherapies for some cancers. Areas covered: New drugs that target distinct steps of the HBV life cycle are been developed, including inhibitors of viral entry, new polymerase inhibitors, capsid and assembly inhibitors, virus release blockers, and disruptors of cccDNA formation and transcription...
May 18, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28515942/a-tandem-cd19-cd20-car-lentiviral-vector-drives-on-target-and-off-target-antigen-modulation-in-leukemia-cell-lines
#13
Dina Schneider, Ying Xiong, Darong Wu, Volker Nӧlle, Sarah Schmitz, Waleed Haso, Andrew Kaiser, Boro Dropulic, Rimas J Orentas
BACKGROUND: Clinical success with chimeric antigen receptor (CAR)- based immunotherapy for leukemia has been accompanied by the associated finding that antigen-escape variants of the disease are responsible for relapse. To target hematologic malignancies with a chimeric antigen receptor (CAR) that targets two antigens with a single vector, and thus potentially lessen the chance of leukemic escape mutations, a tandem-CAR approach was investigated. METHODS: Antigen binding domains from the FMC63 (anti-CD19) and Leu16 (anti-CD20) antibodies were linked in differing configurations to transmembrane and T cell signaling domains to create tandem-CARs...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28515726/comparative-analysis-of-immune-checkpoint-molecules-and-their-potential-role-in-the-transmissible-tasmanian-devil-facial-tumor-disease
#14
Andrew S Flies, Nicholas B Blackburn, Alan Bruce Lyons, John D Hayball, Gregory M Woods
Immune checkpoint molecules function as a system of checks and balances that enhance or inhibit immune responses to infectious agents, foreign tissues, and cancerous cells. Immunotherapies that target immune checkpoint molecules, particularly the inhibitory molecules programmed cell death 1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), have revolutionized human oncology in recent years, yet little is known about these key immune signaling molecules in species other than primates and rodents. The Tasmanian devil facial tumor disease is caused by transmissible cancers that have resulted in a massive decline in the wild Tasmanian devil population...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28515365/ceramide-synthesis-regulates-t-cell-activity-and-gvhd-development
#15
M Hanief Sofi, Jessica Heinrichs, Mohammed Dany, Hung Nguyen, Min Dai, David Bastian, Steven Schutt, Yongxia Wu, Anusara Daenthanasanmak, Salih Gencer, Aleksandra Zivkovic, Zdzislaw Szulc, Holger Stark, Chen Liu, Ying-Jun Chang, Besim Ogretmen, Xue-Zhong Yu
Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective immunotherapy for a variety of hematologic malignances, yet its efficacy is impeded by the development of graft-versus-host disease (GVHD). GVHD is characterized by activation, expansion, cytokine production, and migration of alloreactive donor T cells. Hence, strategies to limit GVHD are highly desirable. Ceramides are known to contribute to inflammation and autoimmunity. However, their involvement in T-cell responses to alloantigens is undefined...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28514453/chromatin-states-define-tumour-specific-t-cell-dysfunction-and-reprogramming
#16
Mary Philip, Lauren Fairchild, Liping Sun, Ellen L Horste, Steven Camara, Mojdeh Shakiba, Andrew C Scott, Agnes Viale, Peter Lauer, Taha Merghoub, Matthew D Hellmann, Jedd D Wolchok, Christina S Leslie, Andrea Schietinger
Tumour-specific CD8 T cells in solid tumours are dysfunctional, allowing tumours to progress. The epigenetic regulation of T cell dysfunction and therapeutic reprogrammability (for example, to immune checkpoint blockade) is not well understood. Here we show that T cells in mouse tumours differentiate through two discrete chromatin states: a plastic dysfunctional state from which T cells can be rescued, and a fixed dysfunctional state in which the cells are resistant to reprogramming. We identified surface markers associated with each chromatin state that distinguished reprogrammable from non-reprogrammable PD1(hi) dysfunctional T cells within heterogeneous T cell populations from tumours in mice; these surface markers were also expressed on human PD1(hi) tumour-infiltrating CD8 T cells...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28513466/non-small-cell-lung-cancer-mutations-targeted-and-combination-therapy
#17
Justyna Kutkowska, Irena Porębska, Andrzej Rapak
Year after year, a growing number of cases of non-small cell lung cancer (NSCLC), mostly caused by smoking, have been noted. Most patients die because of the late detection of cancer and tumor resistance to treatment with cytostatics. Treatment of patients with advanced NSCLC is impeded by the low sensitivity of the tumor to cytostatic agents and the co-existence of many diseases, which substrate is, like lung cancer, cigarette smoking. Along with the development of molecular biology, targeted therapy has started to be used, affecting specific signaling pathways involved in the processes of oncogenesis...
May 17, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28512265/chaetocin-enhances-dendritic-cell-function-via-the-induction-of-heat-shock-protein-and-cancer-testis-antigens-in-myeloma-cells
#18
Manh-Cuong Vo, Thanh-Nhan Nguyen-Pham, Hyun-Ju Lee, Sung-Hoon Jung, Nu-Ri Choi, My-Dung Hoang, Hyeoung-Joon Kim, Je-Jung Lee
Dendritic cells (DC)-based vaccines are considered useful in cancer immuno-therapy, and the interactions of DC and dying tumor cells are important and promising for cancer immunotherapy. We investigated whether chaetocin could be used to induce death of myeloma cells, for loading onto DCs can affect DCs function. In this study, we show that the dying myeloma cells treated with chaetocin resulted in the induction of heat shock protein (HSP) 90, which was inhibited by antioxidant N-acetyl cysteine, and showed an increase in the expression of MAGE-A3 and MAGE-C1/CT7...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28509532/nanodiamonds-mediate-oral-delivery-of-proteins-for-stem-cell-activation-and-intestinal-remodeling-in-drosophila
#19
Xingjie Hu, Xiaojiao Li, Min Yin, Ping Li, Ping Huang, Lihua Wang, Yiguo Jiang, Hui Wang, Nan Chen, Chunhai Fan, Haiyun Song
Introduction of exogenous bio-macromolecules into living systems is of great interest in genome editing, cancer immunotherapy and stem cell reprogramming. Whereas current strategies generally depend on nucleic acids transfection, direct delivery of functional proteins that provides enhanced specificity, increased safety, fast and temporal regulation is highly desirable. Nevertheless, intracellular delivery of intact and bioactive proteins, especially in vivo, remains poorly explored. In this study, we developed a nanodiamonds (NDs)-based protein delivery system in cultured cells and in Drosophila, which showed high adsorption, high efficiency and effective cytosolic release of fully functional proteins...
May 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28508448/a-novel-multi-epitope-vaccine-from-mmsa-1-and-dkk1-for-multiple-myeloma-immunotherapy
#20
Chenyang Lu, Shan Meng, Yanxia Jin, Wanggang Zhang, Zongfang Li, Fang Wang, Feng Wang-Johanning, Yongchang Wei, Hailing Liu, Honglei Tu, Dan Su, Aili He, Xingmei Cao, Fuling Zhou
The identification of novel tumour-associated antigens is urgently needed to improve the efficacy of immunotherapy for multiple myeloma (MM). In this study, we identified a membrane protein MMSA-1 (multiple myeloma special antigen-1) that was specifically expressed in MM and exhibited significantly positive correlation with MM. We then identified HLA-A*0201-restricted MMSA-1 epitopes and tested their cytotoxic T lymphocyte (CTL) response. The MMSA-1 epitope SLSLLTIYV vaccine was shown to induce an obvious CTL response in vitro...
May 16, 2017: British Journal of Haematology
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