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Specific immunotherapy

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https://www.readbyqxmd.com/read/28644608/targeting-cpg-adjuvant-to-lymph-node-via-dextran-conjugate-enhances-anti-tumor-immunotherapy
#1
Weidong Zhang, Myunggi An, Jingchao Xi, Haipeng Liu
Nucleic acids based adjuvants recognized by Toll-like receptors (TLR) are potent immune system stimulants that can augment the anti-tumor immune responses in an antigen-specific manner. However, their clinical uses as vaccine adjuvants are limited primarily due to lack of accumulation in the lymph nodes, the anatomic sites where the immune responses are initiated. Here, we showed that chemical conjugation of type B CpG DNA, a TLR9 agonist to dextran polymer dramatically enhanced CpG's lymph node accumulation in mice...
June 23, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28643325/surface-expression-of-anti-cd3scfv-stimulates-locoregional-immunotherapy-against-hepatocellular-carcinoma-depending-on-the-e1a-engineered-human-umbilical-cord-mesenchymal-stem-cells
#2
Qing Zhang, Xiang-Fei Yuan, Yang Lu, Zhen-Zhen Li, Shi-Qi Bao, Xiao-Long Zhang, Yuan-Yuan Yang, Dong-Mei Fan, Yi-Zhi Zhang, Chen-Xuan Wu, Hong-Xing Guo, Yan-Jun Zhang, Ye Zhou, Dong-Sheng Xiong
Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction...
June 23, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28642820/intratumorally-injected-pro-inflammatory-allogeneic-dendritic-cells-as-immune-enhancers-a-first-in-human-study-in-unfavourable-risk-patients-with-metastatic-renal-cell-carcinoma
#3
Anna Laurell, Maria Lönnemark, Einar Brekkan, Anders Magnusson, Anna Tolf, Anna Carin Wallgren, Bengt Andersson, Lars Adamson, Rolf Kiessling, Alex Karlsson-Parra
BACKGROUND: Accumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28642246/modulation-of-endoplasmic-reticulum-stress-controls-cd4-t-cell-activation-and-anti-tumor-function
#4
Jessica E Thaxton, Caroline Wallace, Brian Riesenberg, Yongliang Zhang, Chrystal Paulos, Craig Beeson, Bei Liu, Zihai Li
The endoplasmic reticulum (ER) is an energy-sensing organelle with intimate ties to programming cell activation and metabolic fate. T-cell receptor (TCR) activation represents a form of acute cell stress and induces mobilization of ER Ca(2+) stores. The role of the ER in programming T-cell activation and metabolic fate remains largely undefined. Gp96 is an ER protein with functions as a molecular chaperone and Ca(2+) buffering protein. We hypothesized that the ER stress response may be important for CD4(+) T-cell activation and that gp96 may be integral to this process...
June 22, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28641998/construction-of-a-hepatitis-b-virus-neutralizing-chimeric-monoclonal-antibody-recognizing-escape-mutants-of-the-viral-surface-antigen-hbsag
#5
Forough Golsaz-Shirazi, Mohammad Mehdi Amiri, Samira Farid, Motahareh Bahadori, Felix Bohne, Sebastian Altstetter, Lisa Wolff, Tohid Kazemi, Jalal Khoshnoodi, Mohammad Hojjat-Farsangi, Michael Chudy, Mahmood Jeddi-Tehrani, Ulrike Protzer, Fazel Shokri
Hepatitis B virus (HBV) infection is a global burden on the health-care system and is considered as the tenth leading cause of death in the world. Over 248 million patients are currently suffering from chronic HBV infection worldwide and annual mortality rate of this infection is 686000. The "a" determinant is a hydrophilic region present in all antigenic subtypes of hepatitis B surface antigen (HBsAg), and antibodies against this region can neutralize the virus and are protective against all subtypes. We have recently generated a murine anti-HBs monoclonal antibody (4G4), which can neutralize HBV infection in HepaRG cells and recognize most of the escape mutant forms of HBsAg...
June 19, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28641531/application-of-alphaviral-vectors-for-immunomodulation-in-cancer-therapy
#6
Anna Zajakina, Karina Spunde, Kenneth Lundstrom
BACKGROUND: The lack of specific and efficient cancer therapies has influenced the development of novel approaches, such as immunotherapy, which from its original application of immunogenic protein delivery has developed into the use of more sophisticated recombinant gene delivery methods to achieve better safety and efficacy profiles. This approach involves viral and non-viral delivery systems. METHODS: Expression vectors have been engineered for alphaviruses, including Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus...
June 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28638730/blockade-of-only-tgf-%C3%AE-1-and-2-is-sufficient-to-enhance-the-efficacy-of-vaccine-and-pd-1-checkpoint-blockade-immunotherapy
#7
Masaki Terabe, Faith C Robertson, Katharine Clark, Emma De Ravin, Anja Bloom, David J Venzon, Shingo Kato, Amer Mirza, Jay A Berzofsky
Checkpoint inhibition has established immunotherapy as a major modality of cancer treatment. However, the success of cancer immunotherapy is still limited as immune regulation of tumor immunity is very complicated and mechanisms involved may also differ among cancer types. Beside checkpoints, other good candidates for immunotherapy are immunosuppressive cytokines. TGF-β is a very potent immunosuppressive cytokine involved in suppression of tumor immunity and also necessary for the function of some regulatory cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638381/anti-bovine-programmed-death-1-rat-bovine-chimeric-antibody-for-immunotherapy-of-bovine-leukemia-virus-infection-in-cattle
#8
Tomohiro Okagawa, Satoru Konnai, Asami Nishimori, Naoya Maekawa, Ryoyo Ikebuchi, Shinya Goto, Chie Nakajima, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
Blockade of immunoinhibitory molecules, such as programmed death-1 (PD-1)/PD-ligand 1 (PD-L1), is a promising strategy for reinvigorating exhausted T cells and preventing disease progression in a variety of chronic infections. Application of this therapeutic strategy to cattle requires bovinized chimeric antibody targeting immunoinhibitory molecules. In this study, anti-bovine PD-1 rat-bovine chimeric monoclonal antibody 5D2 (Boch5D2) was constructed with mammalian expression systems, and its biochemical function and antiviral effect were characterized in vitro and in vivo using cattle infected with bovine leukemia virus (BLV)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28638279/preventive-actions-of-allergen-immunotherapy-the-facts-and-the-effects-in-search-of-evidence
#9
REVIEW
Irene Martignago, Cristoforo Incorvaia, Erminia Ridolo
Allergen immunotherapy (AIT) is the only treatment that works on the causes of allergy. Available AIT nowadays are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) for allergic rhinitis and asthma, while for allergy to Hymenoptera venom only subcutaneous route is recommended. A bulk of trials and meta-analyses demonstrated that efficacy and safety of AIT in decreasing allergic clinical symptoms and use of rescue medications, while its preventive capacity is yet under investigation. The most important of these effects is the prevention of potentially fatal anaphylactic reactions to Hymenoptera stings by venom immunotherapy (VIT)...
2017: Clinical and Molecular Allergy: CMA
https://www.readbyqxmd.com/read/28637878/cd4-t-cell-and-nk-cell-interplay-key-to-regression-of-mhc-class-i-low-tumors-upon-tlr7-8-agonist-therapy
#10
Elien M Doorduijn, Marjolein Sluijter, Daniela C Salvatori, Serenella Silvestri, Saskia Maas, Ramon Arens, Ferry Ossendorp, Sjoerd H van der Burg, Thorbald van Hall
One of the next challenges in cancer immunotherapy is the resistance of tumors to T cell-based treatments through loss of MHC class I. Here, we show that under these circumstances, the Toll-like receptor (TLR)-7/8 ligand imiquimod, but not the TLR3 ligand poly I:C or TLR9 ligand CpG, mediated an effective antitumor response. The rejection of these immune-escaped cancers was mediated by NK cells and CD4(+) T cells, whereas activated CD8(+) T cells were dispensable. Application of the innate immune stimulator at a distant site activated NK cells and thereby elicited tumor-specific T-cell responses in tumor-bearing mice...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28637877/ex-vivoexpanded-adaptive-nk-cells-effectively-kill-primary-acute-lymphoblastic-leukemia-cells
#11
Lisa L Liu, Vivien Beziat, Vincent Oei Yi Sheng, Aline Pfefferle, Marie Schaffer, Soren Lehmann, Eva Hellstrom-Lindberg, Stefan Soderhall, Mats Heyman, Dan Grander, Karl-Johan Malmberg
Manipulation of human NK cell repertoires promises more effective strategies for NK cell-based cancer immunotherapy. A subset of highly differentiated NK cells, termed adaptive NK cells, expands naturally in vivo in response to human cytomegalovirus (HCMV) infection, carries unique repertoires of inhibitory killer cell immunoglobulin-like receptors (KIRs), and displays strong cytotoxicity against tumor cells. Here, we established a robust and scalable protocol for ex vivo generation and expansion of adaptive NK cells for cell therapy against pediatric acute lymphoblastic leukemia (ALL)...
June 21, 2017: Cancer Immunology Research
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
#12
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
#13
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/28634084/drug-delivery-to-melanoma-brain-metastases-can-current-challenges-lead-to-new-opportunities
#14
Gautham Gampa, Shruthi Vaidhyanathan, Jann N Sarkaria, William F Elmquist
Melanoma has a high propensity to metastasize to the brain, and patients with melanoma brain metastases (MBM) have an extremely poor prognosis. The recent approval of several molecularly-targeted agents (e.g., BRAF, MEK inhibitors) and biologics (anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies) has brought new hope to patients suffering from this formerly untreatable and lethal disease. Importantly, there have been recent reports of success in some clinical studies examining the efficacy of both targeted agents and immunotherapies that show similar response rates in both brain metastases and extracranial disease...
June 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28633520/ion-selective-nanosensor-for-photoacoustic-and-fluorescence-imaging-of-potassium
#15
Chang Heon Lee, Jeff Folz, Wuliang Zhang, Janggun Jo, Joel W Y Tan, Xueding Wang, Raoul Kopelman
Ion-selective optodes (ISOs), the optical analog of ion-selective electrodes, have played an increasingly important role in chemical and biochemical analysis. Here we extend this technique to ion-selective photo-acoustic optodes (ISPAOs) that serve at the same time as fluorescence-based ISOs, and apply it specifically to potassium (K+). Notably, the potassium ion is one of the most abundant cations in biological systems, involved in numerous physiological and pathological processes. Furthermore, it has been recently reported that the presence of abnormal extracellular potassium concentrations in tumors suppresses the immune responses and thus suppresses immunotherapy...
June 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28633319/immunotherapy-targeting-adenosine-synthase-a-decreases-severity-of-staphylococcus-aureus-infection-in-mouse-model
#16
Bao-Zhong Zhang, JianPiao Cai, Bin Yu, Lifeng Xiong, Qiubin Lin, Xiao-Yan Yang, Chen Xu, SongYue Zheng, Richard Yi-Tsun Kao, Konghung Sze, Kwok-Yung Yuen, Jian-Dong Huang
Staphylococcus aureus (S. aureus) is a severe pathogen found in the community and in hospitals. Most notably, Methicillin-resistant S. aureus (MRSA) is resistant to almost all antibiotics, which is a growing public health concern. The emergence of drug-resistant strains has prompted the search for alternative treatments such as immunotherapeutic approaches. Previous research showed that S. aureus exploit the immunomodulatory attributes of adenosine to escape host immunity. In this study, we investigated adenosine synthase A (AdsA), a S...
June 13, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28632692/improved-123i-ioflupane-binding-after-immunotherapy-in-anti-nae-antibody-positive-hashimoto-encephalopathy-that-clinically-mimicked-multiple-system-atrophy
#17
Juuri Otsuka, Ayumi Hida, Kamiyu Ogyu, Ryogo Minamimoto, Sousuke Takeuchi
We describe an 84-year-old man with anti-NH2-terminal of α-enolase antibody-positive Hashimoto encephalopathy that clinically mimicked multiple system atrophy who underwent investigation by dopamine transporter SPECT before and after immunotherapy. Before treatment, dopamine transporter SPECT showed reduced striatal I-ioflupane binding, with a mean specific binding ratio of 2.42, even though he had no apparent parkinsonism. After immunotherapy, mean specific binding ratio was improved to 3.22. Dopamine transporter SPECT was useful in this case to detect subclinical striatal dysfunction, and evaluation both before and after immunotherapy helped to distinguish between neurodegenerative disease and neuroimmunological disorder...
June 19, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28630682/overexpressed-prame-is-a-potential-immunotherapy-target-in-sarcoma-subtypes
#18
Jason Roszik, Wei-Lien Wang, John A Livingston, Christina L Roland, Vinod Ravi, Cassian Yee, Patrick Hwu, Andrew Futreal, Alexander J Lazar, Shreyaskumar R Patel, Anthony P Conley
BACKGROUND: PRAME (preferentially expressed antigen in melanoma), a member of the cancer-testis antigen family, has been shown to have increased expression in solid tumors, including sarcoma, and PRAME-specific therapies are currently in development for other cancers such as melanoma. METHODS: To map the landscape of PRAME expression in sarcoma, we used publicly available data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) projects and determined which sarcoma subtypes and subsets are associated with increased PRAME expression...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28630381/antibody-response-to-human-extracellular-her2-subdomain-proteins-in-mice
#19
Fateme Sadri-Ardalani, Moslem Ahmadi, Azam Hemmati, Shaghayegh Emami, Samira Farid, Mohammad Mehdi Amiri, Mahmood Jeddi-Tehrani, Mahdi Shabani, Fazel Shokri
BACKGROUND: In addition to passive immunotherapy using anti-HER2 monoclonal antibodies, active immunotherapy via HER2 targeting is an interesting approach to inducing specific anti-tumor immune responses. We have recently reported the immunogenicity of HER2 subdomains following DNA immunization and HER2 protein boosting. In the present study, we evaluated the immunogenicity of different HER2 extracellular subdomains for the induction of anti-HER2 antibody response in BALB/c mice. OBJECTIVE: To investigate and characterize antibody responses to human recombinant proteins of HER2 extracellular subdomains in immunized mice...
June 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28630228/the-achilles-heel-of-cancer-and-its-implications-for-the-development-of-novel-immunotherapeutic-strategies
#20
Kroopa Joshi, Benjamin M Chain, Karl S Peggs, Sergio A Quezada
Over the last century, scientists have embraced the idea of mobilizing antitumor immune responses in patients with cancer. In the last decade, we have seen the rebirth of cancer immunotherapy and its validation in a series of high profile clinical trials following the discovery of several immune-regulatory receptors. Recent studies point toward the tumor mutational load and resulting neoantigen burden as being crucial to tumor cell recognition by the immune system, highlighting a potentially targetable Achilles heel in cancer...
June 19, 2017: Cold Spring Harbor Perspectives in Medicine
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