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https://www.readbyqxmd.com/read/28337438/mage-a-antigens-and-cancer-immunotherapy
#1
Paul Zajac, Elke Schultz-Thater, Luigi Tornillo, Charlotte Sadowski, Emanuele Trella, Chantal Mengus, Giandomenica Iezzi, Giulio C Spagnoli
MAGE-A antigens are expressed in a variety of cancers of diverse histological origin and germinal cells. Due to their relatively high tumor specificity, they represent attractive targets for active specific and adoptive cancer immunotherapies. Here, we (i) review past and ongoing clinical studies targeting these antigens, (ii) analyze advantages and disadvantages of different therapeutic approaches, and (iii) discuss possible improvements in MAGE-A-specific immunotherapies.
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28337200/metabolic-hallmarks-of-tumor-and-immune-cells-in-the-tumor-microenvironment
#2
REVIEW
Kathrin Renner, Katrin Singer, Gudrun E Koehl, Edward K Geissler, Katrin Peter, Peter J Siska, Marina Kreutz
Cytotoxic T lymphocytes and NK cells play an important role in eliminating malignant tumor cells and the number and activity of tumor-infiltrating T cells represent a good marker for tumor prognosis. Based on these findings, immunotherapy, e.g., checkpoint blockade, has received considerable attention during the last couple of years. However, for the majority of patients, immune control of their tumors is gray theory as malignant cells use effective mechanisms to outsmart the immune system. Increasing evidence suggests that changes in tumor metabolism not only ensure an effective energy supply and generation of building blocks for tumor growth but also contribute to inhibition of the antitumor response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28337197/hypofractionated-irradiation-has-immune-stimulatory-potential-and-induces-a-timely-restricted-infiltration-of-immune-cells-in-colon-cancer-tumors
#3
Benjamin Frey, Michael Rückert, Julia Weber, Xaver Mayr, Anja Derer, Michael Lotter, Christoph Bert, Franz Rödel, Rainer Fietkau, Udo S Gaipl
In addition to locally controlling the tumor, hypofractionated radiotherapy (RT) particularly aims to activate immune cells in the RT-modified microenvironment. Therefore, we examined whether hypofractionated RT can activate dendritic cells (DCs), induce immune cell infiltration in tumors, and how the chronology of immune cell migration into tumors occurs to gain knowledge for future definition of radiation breaks and inclusion of immunotherapy. Colorectal cancer treatments offer only limited survival benefit, and immunobiological principles for additional therapies need to be explored with preclinical models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28336893/chitosan-functionalized-graphene-oxide-as-a-potential-immunoadjuvant
#4
Ting Yan, Huijie Zhang, Dandi Huang, Shini Feng, Morihisa Fujita, Xiao-Dong Gao
The application of graphene oxide (GO) as a potential vaccine adjuvant has recently attracted considerable attention. However, appropriate surface functionalization of GO is crucial to improve its biocompatibility and enhance its adjuvant activity. In this study, we developed a simple method to prepare chitosan (CS)-functionalized GO (GO-CS) and further investigated its potential as a nanoadjuvant. Compared with GO, GO-CS possessed considerably smaller size, positive surface charge, and better thermal stability...
March 8, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28336379/synthetic-nanovaccines-for-immunotherapy
#5
Min Luo, Layla Z Samandi, Zhaohui Wang, Zhijian J Chen, Jinming Gao
Although vaccination is historically one of the most successful strategies for the prevention of infectious diseases, development of vaccines for cancer and many chronic infections, such as HIV, malaria, and tuberculosis, has remained a challenge. Strong and long-lasting antigen-specific T cell responses are critical for therapy of these diseases. A major challenge in achieving a robust CD8+ T cell response is the requirement of spatio-temporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation...
March 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28336378/optimized-biodegradable-polymeric-reservoir-mediated-local-and-sustained-co-delivery-of-dendritic-cells-and-oncolytic-adenovirus-co-expressing-il-12-and-gm-csf-for-cancer-immunotherapy
#6
Eonju Oh, Jung-Eun Oh, JinWoo Hong, YoonHo Chung, Yunki Lee, Ki Dong Park, Sungwan Kim, Chae-Ok Yun
Administration of dendritic cells (DCs) combined with oncolytic adenovirus (Ad) expressing antitumor cytokines induces a potent antitumor effect and antitumor immunity by ameliorating the immunosuppressive tumor microenvironment. However, this combination therapy has significant limitations due to rapid dissemination and inactivation of the therapeutics at the tumor site, necessitating multiple injections of both therapeutics. To overcome these limitations, we have utilized gelatin-based hydrogel to co-deliver oncolytic Ad co-expressing interleukin (IL)-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) (oAd) and DCs for sustained release of both therapeutics...
March 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28336309/usefulness-of-the-ellipro-epitope-predictor-program-in-defining-the-repertoire-of-hla-abc-eplets
#7
Rene J Duquesnoy, Marilyn Marrari
HLA matching at the epitope level offers new opportunities to identify suitable donors for transplant patients. The International HLA Epitope Registry (www.Epregistry.com.br) describes for the various HLA loci, repertoires of eplets including those that correspond to epitopes experimentally verified with specific antibodies. There are also many eplets which have remained as theoretical entities because no informative antibodies have been found. Which of them have immunogenic potential or conversely, might be considered as non-epitopes that cannot elicit specific antibody responses? This question is important for the application of epitope-based HLA matching in clinical transplantation...
March 20, 2017: Human Immunology
https://www.readbyqxmd.com/read/28335643/prospects-and-progress-of-atezolizumab-in-non-small-cell-lung-cancer
#8
Johan Vansteenkiste, Els Wauters, Keunchil Park, Achim Rittmeyer, Alan Sandler, Alexander Spira
Immunotherapy has recently come to the forefront of oncology treatment as a potential means of combating cancer by restoring the body's adaptive cancer-immunity cycle. Atezolizumab is a monoclonal antibody agent that specifically targets programmed death ligand 1 (PD-L1), a key molecule in the cancer-immunity pathway, to block binding to its receptors PD-1 and B7.1. Areas covered: This review covers the role of atezolizumab in the treatment of non-small-cell lung cancer (NSCLC). Several studies have reported promising efficacy in this indication...
March 24, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28333360/gammadelta-t-cells-in-crohn-s-disease-a-new-player-in-the-disease-pathogenesis
#9
Catalan-Serra Ignacio, Arne Kristian Sandvik, Torunn Bruland, Juan Carlos Andreu-Ballester
Crohn's disease (CD) is a chronic relapsing systemic disease affecting the gastrointestinal tract. An altered immune response to commensal intestinal bacteria takes place in genetically predisposed individuals, resulting in chronic inflammation in the gut. Several alterations in the innate immunity mechanisms have been described in recent years. Thus, the study of the immunological aspects of CD, specifically the role of lymphocytes, is a key element for understanding the pathogenesis of the disease. Gammadelta T cells (γδ T cells) constitute only a small proportion of the lymphocytes that circulate in the blood and peripheral organs and they are present mainly in the epithelia, where they can constitute up to 40% of intraepithelial lymphocytes (IEL) in the intestinal mucosa...
March 16, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28332627/cross-neutralizing-anti-hiv-1-human-single-chain-variable-fragments-scfvs-against-cd4-binding-site-and-n332-glycan-identified-from-a-recombinant-phage-library
#10
Lubina Khan, Rajesh Kumar, Ramachandran Thiruvengadam, Hilal Ahmad Parray, Muzamil Ashraf Makhdoomi, Sanjeev Kumar, Heena Aggarwal, Madhav Mohata, Abdul Wahid Hussain, Raksha Das, Raghavan Varadarajan, Jayanta Bhattacharya, Madhu Vajpayee, K G Murugavel, Suniti Solomon, Subrata Sinha, Kalpana Luthra
More than 50% of HIV-1 infection globally is caused by subtype_C viruses. Majority of the broadly neutralizing antibodies (bnAbs) targeting HIV-1 have been isolated from non-subtype_C infected donors. Mapping the epitope specificities of bnAbs provides useful information for vaccine design. Recombinant antibody technology enables generation of a large repertoire of monoclonals with diverse specificities. We constructed a phage recombinant single chain variable fragment (scFv) library with a diversity of 7.8 × 10(8) clones, using a novel strategy of pooling peripheral blood mononuclear cells (PBMCs) of six select HIV-1 chronically infected Indian donors whose plasma antibodies exhibited potent cross neutralization efficiency...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332095/identification-of-t-cell-target-antigens-in-glioblastoma-stem-like-cells-using-an-integrated-proteomics-based-approach-in-patient-specimens
#11
Carmen Rapp, Rolf Warta, Slava Stamova, Ali Nowrouzi, Christoph Geisenberger, Zoltan Gal, Saskia Roesch, Steffen Dettling, Simone Juenger, Mariana Bucur, Christine Jungk, Philip DaoTrong, Rezvan Ahmadi, Felix Sahm, David Reuss, Valentina Fermi, Esther Herpel, Volker Eckstein, Niels Grabe, Christoph Schramm, Markus A Weigand, Juergen Debus, Andreas von Deimling, Andreas Unterberg, Amir Abdollahi, Philipp Beckhove, Christel Herold-Mende
Glioblastoma (GBM) is a highly aggressive brain tumor and still remains incurable. Among others, an immature subpopulation of self-renewing and therapy-resistant tumor cells-often referred to as glioblastoma stem-like cells (GSCs)-has been shown to contribute to disease recurrence. To target these cells personalized immunotherapy has gained a lot of interest, e.g. by reactivating pre-existing anti-tumor immune responses against GSC antigens. To identify T cell targets commonly presented by GSCs and their differentiated counterpart, we used a proteomics-based separation of GSC proteins in combination with a T cell activation assay...
March 22, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28331615/nuclear-irf-1-expression-as-a-mechanism-to-assess-capability-to-express-pd-l1-and-response-to-pd-1-therapy-in-metastatic-melanoma
#12
James W Smithy, Lauren M Moore, Vasiliki Pelekanou, Jamaal Rehman, Patricia Gaule, Pok Fai Wong, Veronique M Neumeister, Mario Sznol, Harriet M Kluger, David L Rimm
BACKGROUND: Predictive biomarkers for antibodies against programmed death 1 (PD-1) remain a major unmet need in metastatic melanoma. Specifically, response is seen in tumors that do not express programmed death ligand 1 (PD-L1), highlighting the need for a more sensitive biomarker. We hypothesize that capacity to express PD-L1, as assessed by an assay for a PD-L1 transcription factor, interferon regulatory factor 1 (IRF-1), may better distinguish patients likely to benefit from anti-PD-1 immunotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28331613/systematic-evaluation-of-immune-regulation-and-modulation
#13
REVIEW
David F Stroncek, Lisa H Butterfield, Michael A Cannarile, Madhav V Dhodapkar, Tim F Greten, Jean Charles Grivel, David R Kaufman, Heidi H Kong, Firouzeh Korangy, Peter P Lee, Francesco Marincola, Sergio Rutella, Janet C Siebert, Giorgio Trinchieri, Barbara Seliger
Cancer immunotherapies are showing promising clinical results in a variety of malignancies. Monitoring the immune as well as the tumor response following these therapies has led to significant advancements in the field. Moreover, the identification and assessment of both predictive and prognostic biomarkers has become a key component to advancing these therapies. Thus, it is critical to develop systematic approaches to monitor the immune response and to interpret the data obtained from these assays. In order to address these issues and make recommendations to the field, the Society for Immunotherapy of Cancer reconvened the Immune Biomarkers Task Force...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28330473/dynamic-and-specific-immune-responses-against-multiple-tumor-antigens-were-elicited-in-patients-with-hepatocellular-carcinoma-after-cell-based-immunotherapy
#14
Yanyan Han, Yeting Wu, Chou Yang, Jing Huang, Yabing Guo, Li Liu, Ping Chen, Dongyun Wu, Junyun Liu, Jin Li, Xiangjun Zhou, Jinlin Hou
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in China and frequently occurs with chronic hepatitis B virus infection. To investigate whether cell-based cancer immunotherapy induces tumor specific immune responses in patients with HCC and provides clinical benefits, as well as to elucidate the most immunogenic tumor associated antigens (TAAs), multiple antigen stimulating cellular therapy (MASCT) was applied in addition to standard of care. METHODS: Mature dendritic cells (DCs) and activated T cells prepared for MASCT were generated from autologous peripheral blood mononuclear cells (PBMCs)...
March 22, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28330372/car-t-cell-therapy-progress-and-prospects
#15
Olivia Wilkins, Allison May Keeler, Terence R Flotte
Lentivirus-mediated transduction of autologous T-cells with a chimeric antigen receptor (CAR) to confer a desired epitope-specificity as a targeted immunotherapy for cancer has been among the first human gene therapy techniques to demonstrate widespread therapeutic efficacy. Other approaches to using gene therapy to enhance anti-tumor immunity have been less specific and less effective. These included amplification, marking, and cytokine transduction of tumor infiltrating lymphocytes (TIL), recombinant virus-based expression of tumor antigens as a tumor vaccine, and transduction of antigen-presenting cells (APCs) with tumor antigens...
March 23, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28329770/antigen-presentation-profiling-reveals-recognition-of-lymphoma-immunoglobulin-neoantigens
#16
Michael S Khodadoust, Niclas Olsson, Lisa E Wagar, Ole A W Haabeth, Binbin Chen, Kavya Swaminathan, Keith Rawson, Chih Long Liu, David Steiner, Peder Lund, Samhita Rao, Lichao Zhang, Caleb Marceau, Henning Stehr, Aaron M Newman, Debra K Czerwinski, Victoria E H Carlton, Martin Moorhead, Malek Faham, Holbrook E Kohrt, Jan Carette, Michael R Green, Mark M Davis, Ronald Levy, Joshua E Elias, Ash A Alizadeh
Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. However, the personalized identification and validation of neoantigens remains a major challenge. Here we discover neoantigens in human mantle-cell lymphomas by using an integrated genomic and proteomic strategy that interrogates tumour antigen peptides presented by major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically characterize MHC ligands from 17 patients...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28328317/antiproliferative-and-apoptotic-effects-of-novel-anti-ror1-single-chain-antibodies-in-hematological-malignancies
#17
Leili Aghebati-Maleki, Vahid Younesi, Behzad Baradaran, Jalal Abdolalizadeh, Morteza Motallebnezhad, Hamid Nickho, Dariush Shanehbandi, Jafar Majidi, Mehdi Yousefi
Receptor tyrosine kinase-like orphan receptor (ROR) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including cell survival, differentiation, cell migration, cell communication, cell polarity, proliferation, metabolism, and angiogenesis. ROR1 has recently been shown to be expressed in various types of cancer cells but not normal cells. Pharmacokinetics and pharmacodynamics of single-chain Fragment variable (scFv) antibodies provide potential therapeutic advantages over whole antibody molecules...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28327987/pssmhcpan-a-novel-pssm-based-software-for-predicting-class-i-peptide-hla-binding-affinity
#18
Geng Liu, Dongli Li, Zhang Li, Si Qiu, Wenhui Li, Cheng-Chi Chao, Naibo Yang, Handong Li, Zhen Cheng, Xin Song, Le Cheng, Xiuqing Zhang, Jian Wang, Huanming Yang, Kun Ma, Yong Hou, Bo Li
Background: Predicting peptides binding affinity with human leukocyte antigen (HLA) is a crucial step in developing powerful antitumor vaccine for cancer immunotherapy. Currently available methods work quite well in predicting peptide binding affinity with HLA alleles such as HLA-A*0201, HLA-A*0101, and HLA-B*0702 in terms of sensitivity and specificity. However, quite a few types of HLA alleles that are present in majority of human populations including HLA-A*0202, HLA-A*0203, HLA-A*6802, HLA-B*5101, HLA-B*5301, HLA-B*5401 and HLA-B*5701 still cannot be predicted with satisfactory accuracy using currently available methods...
March 15, 2017: GigaScience
https://www.readbyqxmd.com/read/28327924/long-term-outcome-of-487-patients-with-early-stage-extra-nodal-marginal-zone-lymphoma
#19
S Teckie, S Qi, M Chelius, S Lovie, M Hsu, A Noy, C Portlock, J Yahalom
Background: Localized early-stage extra-nodal marginal zone lymphoma (MZL) presents with heterogeneous organ involvement and is treated with various modalities, including resection, radiotherapy, and systemic therapy. We report the long-term outcome of a large cohort of extra-nodal MZL and assess the impact of patient and disease characteristics, organ site, and treatment strategy on disease control and survival. Patients and Methods: We identified 487 consecutive patients with stage IE or IIE MZL referred between 1992 and 2012 to Memorial Sloan Kettering Cancer Center...
January 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28325250/radiotherapy-in-the-age-of-cancer-immunology-current-concepts-and-future-developments
#20
REVIEW
Mauro Loi, Isacco Desideri, Daniela Greto, Monica Mangoni, Mariangela Sottili, Icro Meattini, Carlotta Becherini, Francesca Terziani, Camilla Delli Paoli, Emanuela Olmetto, Pierluigi Bonomo, Lorenzo Livi
Major advances in the knowledge of cancer biology and its interactions with tumor immune environment led to the emergence, in the last five years of new immunotherapy-based treatment strategies in cancer patients. At the same time, improvement in radiation technique and progress in radiobiology allowed in the last decade to expand the applications of radiotherapy in a growing number of settings. At present, there are strong theoretical basis to propose immune-enhanced radiation therapy that may represent in the future a new paradigm of treatment, combining the intrinsic power of radiotherapy to elicit a specific, systemic, tumor-directed immune response with modern highly conformal and precise dose delivery, in order to maximize response at the major site of disease and obtain durable disease control...
April 2017: Critical Reviews in Oncology/hematology
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