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Tumor immunotherapy

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https://www.readbyqxmd.com/read/28343015/systemic-delivery-of-the-tumor-necrosis-factor-gene-to-tumors-by-a-novel-dual-dna-nanocomplex-in-a-nanoparticle-system
#1
Vasundhara Shukla, Manu Dalela, Manika Vij, Munia Ganguli, Ralph Weichselbaum, Surender Kharbanda, Donald Kufe, Harpal Singh
Many cancers fail to respond to immunotherapy as a result of immune suppression by the tumor microenvironment. The exogenous expression of immune cytokines to reprogram the tumor microenvironment represents an approach to circumvent this suppression. The present studies describe the development of a novel dual nanoparticle (DNP) system for driving DNA expression vectors encoding inflammatory cytokines in tumor cells. The DNP system consists of a DNA expression vector-cationic nanocomplex (NC) surrounded by a diblock polymeric NP...
March 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28339788/intravenous-dendritic-cell-administration-enhances-suppression-of-lung-metastasis-induced-by-carbon-ion-irradiation
#2
Ken Ando, Hidetoshi Fujita, Akihiro Hosoi, Liqiu Ma, Masaru Wakatsuki, Ken-Ichiro Seino, Kazuhiro Kakimi, Takashi Imai, Takashi Shimokawa, Takashi Nakano
Carbon-ion radiotherapy (CIRT) is an advanced radiotherapy and has achieved good local control, even in tumors that are resistant to conventional photon beam radiotherapy (PBRT). However, distant metastasis control is an important issue. Recently, the combination of radiotherapy and immunotherapy has attracted the attention. In immunotherapy, dendritic cells (DCs) play a pivotal role in the anti-tumor immune system. However, the mechanisms underlying the combination therapy of DCs and radiotherapy have been unclear...
February 27, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28339493/timely-meta-analysis-on-the-efficacy-of-adoptive-immunotherapy-for-hepatocellular-carcinoma-patients-after-curative-therapy
#3
Han-Yue Mo, Ying-Yang Liao, Xue-Mei You, Alessandro Cucchetti, Bao-Hong Yuan, Ru-Hong Li, Jian-Hong Zhong, Le-Qun Li
AIMS: The role of adoptive immunotherapy (AIT) for patients with hepatocellular carcinoma (HCC) who have received curative therapy is still not well illustrated. This timely meta-analysis aims to update the current evidence on efficacy and safety of AIT for patients with HCC who have received curative therapy. METHODS: We searched PubMed, EMBASE, Scopus and the Cochrane Library Through January 2017 for relevant studies. Mortality and tumor recurrence were compared between patients with or without adjuvant AIT...
2017: PloS One
https://www.readbyqxmd.com/read/28338569/case-report-immune-mediated-complete-response-in-a-patient-with-recurrent-advanced-ewing-sarcoma-ews-after-vigil-immunotherapy
#4
Maurizio Ghisoli, McCarley Rutledge, Philip J Stephens, Robert Mennel, Minal Barve, Meghan Manley, Bahram R Oliai, Kathleen M Murphy, Luisa Manning, Belen Gutierrez, Priyanka Rangadass, Ashli Walker, Zhaohui Wang, Donald Rao, Ned Adams, Gladice Wallraven, Neil Senzer, John Nemunaitis
Ewing sarcoma is a highly resistant disease with a <10% chance of survival at 5 years after failure of frontline chemotherapy. This is a case report of an Ewing sarcoma patient with metastatic disease recurrence <2 years after standard chemotherapy/radiation who achieved a durable and sustained complete response after 2 series of treatments with Vigil (GMCSF/bi-shRNA furin DNA autologous tumor immunotherapy) serially manufactured from first and second recurrences with ELISPOT assay correlation. Results support justification of further testing of Vigil with ELISPOT assay as a biomarker to assess level of immune response and correlation with disease control...
March 23, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28337438/mage-a-antigens-and-cancer-immunotherapy
#5
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
#6
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
#7
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/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
#8
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/28334399/association-of-hiv-status-with-local-immune-response-to-anal-squamous-cell-carcinoma-implications-for-immunotherapy
#9
Elizabeth L Yanik, Genevieve J Kaunitz, Tricia R Cottrell, Farah Succaria, Tracee L McMiller, Maria L Ascierto, Jessica Esandrio, Haiying Xu, Aleksandra Ogurtsova, Toby Cornish, Evan J Lipson, Suzanne L Topalian, Eric A Engels, Janis M Taube
Importance: The programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway play an important immunosuppressive role in cancer and chronic viral infection, and have been effectively targeted in cancer therapy. Anal squamous cell carcinoma (SCC) is associated with both human papillomavirus and HIV infection. To date, patients with HIV have been excluded from most trials of immune checkpoint blocking agents, such as anti-PD-1 and anti-PD-L1, because it was assumed that their antitumor immunity was compromised compared with immunocompetent patients...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28334324/understanding-the-genetic-landscape-of-small-cell-carcinoma-of-the-urinary-bladder-and-implications-for-diagnosis-prognosis-and-treatment-a-review
#10
Erik J Kouba, Liang Cheng
Importance: Small cell carcinoma of the urinary bladder is a rare and aggressive neuroendocrine tumor of the urinary bladder. Although research has been performed since the first case was reported in 1981, most of our understanding of the disease treatments has been extrapolated from small cell carcinoma of the lung. However, current data on patient survival have been stagnant. Observations: With the advent of advanced molecular diagnostic methods, a new potential for understanding the origin and treatment of small cell carcinoma of the urinary bladder has become evident...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28332219/targeting-immunotherapy-to-the-tumor-microenvironment
#11
Michael Dougan, Stephanie K Dougan
Targeting drugs to the tumor microenvironment has long been appreciated as a means of increasing local concentrations and decreasing systemic toxicities. How drug targeting might apply to immune-based therapies is less clear. In this review, we explain the immunology of cancer, with a focus on the principles of in situ vaccination. Certain types of therapies are more amenable to local versus systemic delivery; these include cytokines, adjuvants, radiation, and agents targeting tumor-resident cell populations...
March 23, 2017: Journal of Cellular Biochemistry
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
#12
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/28331617/current-approaches-to-increase-car-t-cell-potency-in-solid-tumors-targeting-the-tumor-microenvironment
#13
REVIEW
Irene Scarfò, Marcela V Maus
Chimeric antigen receptor (CAR) T-cell therapy represents a revolutionary treatment for haematological malignancies (i.e. B-ALL). However, the success of this type of treatment has not yet been achieved in solid tumors. One hypothesis is that the immunosuppressive nature of the tumor microenvironment (TME) influences and affects the efficacy of adoptive immunotherapy. Understanding the role of the TME and its interaction with CAR T-cells is crucial to improve the potency of adoptive immunotherapy. In this review, we discuss the strategies and potential combinatorial approaches recently developed in mouse models to enhance the efficacy of CAR T-cells, with particular emphasis on the translational potential of these approaches...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28331616/ex-vivo-akt-inhibition-promotes-the-generation-of-potent-cd19car-t-cells-for-adoptive-immunotherapy
#14
Ryan Urak, Miriam Walter, Laura Lim, ChingLam W Wong, Lihua E Budde, Sandra Thomas, Stephen J Forman, Xiuli Wang
BACKGROUND: Insufficient persistence and effector function of chimeric antigen receptor (CAR)-redirected T cells have been challenging issues for adoptive T cell therapy. Generating potent CAR T cells is of increasing importance in the field. Studies have demonstrated the importance of the Akt pathway in the regulation of T cell differentiation and memory formation. We now investigate whether inhibition of Akt signaling during ex vivo expansion of CAR T cells can promote the generation of CAR T cells with enhanced antitumor activity following adoptive therapy in a murine leukemia xenograft model...
2017: Journal for Immunotherapy of Cancer
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
#15
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
#16
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/28331101/immunotherapy-of-nivolumab-with-dendritic-cell-vaccination-is-effective-against-intractable-recurrent-primary-central-nervous-system-lymphoma-a-case-report
#17
Motomasa Furuse, Naosuke Nonoguchi, Naoki Omura, Mitsuaki Shirahata, Koichi Iwasaki, Toshio Inui, Toshihiko Kuroiwa, Hiroko Kuwabara, Shin-Ichi Miyatake
We report effective treatment with nivolumab of a patient with recurrent primary central nervous system lymphoma (PCNSL) after multiple therapies. A 41-year-old woman with a right parietal PCNSL underwent treatment with high-dose methotrexate and radiotherapy. After recurrence in the left frontal lobe, the patient received several chemotherapies, including methotrexate and rituximab, and underwent surgery. The tumor was refractory to these treatments, and the patient then underwent intensity-modulated radiotherapy (IMRT)...
March 23, 2017: Neurologia Medico-chirurgica
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
#18
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
#19
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/28327987/pssmhcpan-a-novel-pssm-based-software-for-predicting-class-i-peptide-hla-binding-affinity
#20
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
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