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Dendritic Cell Therapy

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https://www.readbyqxmd.com/read/29334492/anti-il-10-mediated-enhancement-of-antitumor-efficacy-of-a-dendritic-cell-targeting-mip3%C3%AE-gp100-vaccine-in-the-b16f10-mouse-melanoma-model-is-dependent-on-type-i-interferons
#1
James T Gordy, Kun Luo, Brian Francica, Charles Drake, Richard B Markham
The chemokine MIP3α (CCL20) binds to CCR6 on immature dendritic cells. Vaccines fusing MIP3α to gp100 have been shown to be effective in therapeutically reducing melanoma tumor burden and prolonging survival in a mouse model. Other studies have provided evidence that interleukin-10 (IL-10) neutralizing antibodies (αIL-10) enhance immunologic melanoma therapies by modulating the tolerogenic tumor microenvironment. In the current study, we have utilized the B16F10 syngeneic mouse melanoma model to demonstrate for the first time that a therapy neutralizing IL-10 enhances the antitumor efficacy of a MIP3α-gp100 DNA vaccine, leading to significantly smaller tumors, slower growing tumors, and overall increases in mouse survival...
January 12, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29331876/app-go-protein-g%C3%AE-%C3%AE-complex-signaling-mediates-a%C3%AE-degeneration-and-cognitive-impairment-in-alzheimer-s-disease-models
#2
Elena Anahi Bignante, Nicolás Eric Ponce, Florencia Heredia, Juliana Musso, María C Krawczyk, Julieta Millán, Gustavo F Pigino, Nibaldo C Inestrosa, Mariano M Boccia, Alfredo Lorenzo
Deposition of amyloid-β (Aβ), the proteolytic product of the amyloid precursor protein (APP), might cause neurodegeneration and cognitive decline in Alzheimer's disease (AD). However, the direct involvement of APP in the mechanism of Aβ-induced degeneration in AD remains on debate. Here, we analyzed the interaction of APP with heterotrimeric Go protein in primary hippocampal cultures and found that Aβ deposition dramatically enhanced APP-Go protein interaction in dystrophic neurites. APP overexpression rendered neurons vulnerable to Aβ toxicity by a mechanism that required Go-Gβγ complex signaling and p38-mitogen-activated protein kinase activation...
December 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29331323/regulation-of-inflammatory-factors-by-double-stranded-rna-receptors-in-breast-cancer-cells
#3
Amritha Venkatesh, Harika Nandigam, Maria Muccioli, Manindra Singh, Tiffany Loftus, Deana Lewis, Michelle Pate, Fabian Benencia
Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others...
November 22, 2017: Immunobiology
https://www.readbyqxmd.com/read/29331266/human-papilloma-virus-specific-t-cells-can-be-generated-from-na%C3%A3-ve-t-cells-for-use-as-an-immunotherapeutic-strategy-for-immunocompromised-patients
#4
Sarah E McCormack, Conrad Russell Y Cruz, Kaylor E Wright, Allison B Powell, Haili Lang, Cornelia Trimble, Michael D Keller, Ephraim Fuchs, Catherine M Bollard
Human papilloma virus (HPV) is a known cause of cervical cancer, squamous cell carcinoma and laryngeal cancer. Although treatments exist for HPV-associated malignancies, patients unresponsive to these therapies have a poor prognosis. Recent findings from vaccine studies suggest that T-cell immunity is essential for disease control. Because Epstein-Barr Virus (EBV)-specific T cells have been highly successful in treating or preventing EBV-associated tumors, we hypothesized that the development of a manufacturing platform for HPV-specific T cells from healthy donors could be used in a third-party setting to treat patients with high-risk/relapsed HPV-associated cancers...
January 10, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29330750/immunologic-and-gene-expression-profiles-of-spontaneous-canine-oligodendrogliomas
#5
Anna Filley, Mario Henriquez, Tanmoy Bhowmik, Brij Nath Tewari, Xi Rao, Jun Wan, Margaret A Miller, Yunlong Liu, R Timothy Bentley, Mahua Dey
Malignant glioma (MG), the most common primary brain tumor in adults, is extremely aggressive and uniformly fatal. Several treatment strategies have shown significant preclinical promise in murine models of glioma; however, none have produced meaningful clinical responses in human patients. We hypothesize that introduction of an additional preclinical animal model better approximating the complexity of human MG, particularly in interactions with host immune responses, will bridge the existing gap between these two stages of testing...
January 12, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#6
REVIEW
Julian A Marin-Acevedo, Aixa E Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou
Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized...
January 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29318677/antigen-directed-fabrication-of-a-multifunctional-nanovaccine-with-ultrahigh-antigen-loading-efficiency-for-tumor-photothermal-immunotherapy
#7
Jinbin Pan, Yaqiong Wang, Cai Zhang, Xiaoyi Wang, Haoyu Wang, Jiaojiao Wang, Yizhong Yuan, Xu Wang, Xuejun Zhang, Chunshui Yu, Shao-Kai Sun, Xiu-Ping Yan
Current antigen-encapsulated multifunctional nanovaccines for oncotherapy suffer from limited antigen loading efficiency, low yield, tedious manufacture, and systemic toxicity. Here, an antigen-directed strategy for the fabrication of multifunctional nanovaccine with ultrahigh antigen loading efficiency in a facile way for tumor photothermal-immunotherapy is shown. As a proof of concept, a model antigen ovalbumin (OVA) is used as a natural carrier to load a representative theranostic agent indocyanine green (ICG)...
January 10, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29316717/scanning-the-immunopathogenesis-of-psoriasis
#8
REVIEW
Andrea Chiricozzi, Paolo Romanelli, Elisabetta Volpe, Giovanna Borsellino, Marco Romanelli
Psoriasis is a chronic inflammatory skin disease, the immunologic model of which has been profoundly revised following recent advances in the understanding of its pathophysiology. In the current model, a crosstalk between keratinocytes, neutrophils, mast cells, T cells, and dendritic cells is thought to create inflammatory and pro-proliferative circuits mediated by chemokines and cytokines. Various triggers, including recently identified autoantigens, Toll-like receptor agonists, chemerin, and thymic stromal lymphopoietin may activate the pathogenic cascade resulting in enhanced production of pro-inflammatory and proliferation-inducing mediators such as interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-23, IL-22, interferon (IFN)-α, and IFN-γ by immune cells...
January 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29316433/tim-3-regulates-cd103-dendritic-cell-function-and-response-to-chemotherapy-in-breast-cancer
#9
Álvaro de Mingo Pulido, Alycia Gardner, Shandi Hiebler, Hatem Soliman, Hope S Rugo, Matthew F Krummel, Lisa M Coussens, Brian Ruffell
Intratumoral CD103+ dendritic cells (DCs) are necessary for anti-tumor immunity. Here we evaluated the expression of immune regulators by CD103+ DCs in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. Combined efficacy was CD8+ T cell dependent and associated with increased granzyme B expression; however, TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors...
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29306088/changes-in-in-vivo-confocal-microscopic-findings-of-ocular-surface-squamous-neoplasia-during-treatment-with-topical-interferon-alfa-2b
#10
Mehran Zarei-Ghanavati, Ebrahim Mousavi, Amin Nabavi, Golshan Latifi, Hadi Z Mehrjardi, Masoomeh Mohebbi, Hamed Ghassemi, Farrin Mirzaie, Mohammad Ali Zare
PURPOSE: To evaluate in vivo confocal microscopy (IVCM) findings of ocular surface squamous neoplasia (OSSN) during treatment with topical interferon alfa-2b (IFN alfa-2b). METHODS: In this prospective interventional case series, 20 eyes from 20 patients with OSSN were treated with topical IFN alfa-2b 3 million IU/mL four times a day. Treatment was continued for 2 or 3 months after clinical resolution. IVCM was done at baseline, on a monthly basis, and at the end of treatment...
January 3, 2018: Ocular Surface
https://www.readbyqxmd.com/read/29288652/co-activation-of-gr-and-ppar%C3%AE-in-murine-skin-prevents-worsening-of-atopic-march
#11
Julie Deckers, Nadia Bougarne, Viacheslav Mylka, Sofie Desmet, Astrid Luypaert, Michael Devos, Giel Tanghe, Justine Van Moorleghem, Manon Vanheerswynghels, Lode De Cauwer, Jonathan Thommis, Marnik Vuylsteke, Jan Tavernier, Bart Lambrecht, Hamida Hammad, Karolien De Bosscher
Children with atopic dermatitis (AD) show an increased risk to develop asthma later in life, a phenomenon referred to as 'atopic march', which emphasizes the need for secondary prevention therapies. This study aimed to investigate whether relief of skin inflammation by glucocorticoids and PPARγ-agonists might influence the subsequent development of asthma in a murine model for the atopic march in which mice were repeatedly exposed to house dust mite (HDM) via the skin, followed by exposure to HDM in lungs...
December 27, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29285274/lipopolysaccharide-coated-cus-nanoparticles-promoted-anti-cancer-and-anti-metastatic-effect-by-immuno-photothermal-therapy
#12
Bian Jang, Li Xu, Madhappan S Moorthy, Wei Zhang, Ling Zeng, Mingyeong Kang, Minseok Kwak, Junghwan Oh, Jun-O Jin
To meet the ultimate goal of cancer therapy, which is treating not only the primary tumor but also preventing metastatic cancer, the concept of combining immunotherapy with photothermal therapy (PTT) is gaining great interest. Here, we studied the new material, lipopolysaccharide (LPS) coated copper sulfide nanoparticles (LPS-CuS), for the immuno-photothermal therapy. We evaluated the effect of LPS-CuS for induction of apoptosis of CT26 cells and activation of dendritic cells. Moreover, the LPS-CuS and laser irradiation was examined anti-metastasis effect by liver metastasis model mouse in vivo...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29282691/progress-in-vaccine-therapies-for-breast-cancer
#13
Xiaoyu Li, Xia Bu
Therapeutic cancer vaccines aim to treat pre-existing cancer by boosting the patient's own immune system, which is an attractive strategy for cancer treatment. The cancer vaccines have mainly been designed to elicit antitumor T-cell immune responses that recognize and eradicate cancer. The advantages of cancer immunotherapy with cancer vaccines include a) high specificity of tumor antigen, b) minimal vaccine-related adverse events, and c) long-lasting immunity boosted by cancer vaccine which is important to control tumor relapse...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29276510/recent-successes-and-future-directions-in-immunotherapy-of-cutaneous-melanoma
#14
REVIEW
Hassan Sadozai, Thomas Gruber, Robert Emil Hunger, Mirjam Schenk
The global health burden associated with melanoma continues to increase while treatment options for metastatic melanoma are limited. Nevertheless, in the past decade, the field of cancer immunotherapy has witnessed remarkable advances for the treatment of a number of malignancies including metastatic melanoma. Although the earliest observations of an immunological antitumor response were made nearly a century ago, it was only in the past 30 years, that immunotherapy emerged as a viable therapeutic option, in particular for cutaneous melanoma...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29276180/cd40-knocked-down-tolerogenic-dendritic-cells-decrease-diabetic-injury
#15
Aziz Mahmoudzadeh, Ali Akbar Pourfathollah, Mohammad Hossein Karimi, Seyed Mohammad Moazzeni
BACKGROUND: Type-1 diabetes (T1D) is an autoimmune disease in which T lymphocytes destroy insulin-producing β-cells. Control of self-reactive T lymphocytes and recovery of diabetic injury is the end point of T1D. OBJECTIVE: To investigate generation of tolerogenic dendritic cells (tolDCs) as an innovative method of diabetes therapy. METHODS: Lentivirus vector production was achieved by GIPZ mouse CD40 shRNA, psPAX2 and pMD2G plasmids DNA...
December 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/29275468/targeting-myeloid-derived-suppressor-cells-in-cancer
#16
Waseem Anani, Michael R Shurin
Myeloid derived suppressor cells (MDSC) represent only a minor fraction of circulating blood cells but play an important role in tumor formation and progression. They are a heterogeneous group of cells that influence the tumor microenvironment by depletion of amino acids, oxidative stress, decreased trafficking of antitumor effector cells, and increased regulatory T and regulatory dendritic cell responses. Investigational treatment strategies targeting MDSCs have attempted to inhibit MDSC development and expansion (stem cell factor blockade, modulate of cell signaling, and target MDSC migration and recruitment), inhibit MDSC function (nitric oxide inhibition and reactive oxygen and nitrogen species inhibition), differentiate MDSCs into more mature cells (Vitamins A and D, all-trans retinoic acid, interleukin-2, toll-like receptor 9 inhibitors, taxanes, beta-glucan particles, tumor-derived exosome inhibition, and very small size proteoliposomes), and destroy MDSCs (cytotoxic agents, ephrin A2 degradation, anti-interleukin 13, and histamine blockers)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29275461/tumor-immuno-environment-in-cancer-progression-and-therapy
#17
Pawel Kalinski, James E Talmadge
The approvals of Provenge (Sipuleucel-T), Ipilimumab (Yervoy/anti-CTLA-4) and blockers of the PD-1 - PD-L1/PD-L2 pathway, such as nivolumab (Opdivo), pembrolizumab (Keytruda), or atezolizumab (Tecentriq), have established immunotherapy as a key component of comprehensive cancer care. Further, murine mechanistic studies and studies in immunocompromised patients have documented the critical role of immunity in effectiveness of radio- and chemotherapy. However, in addition to the ability of the immune system to control cancer progression, it can also promote tumor growth, via regulatory T cells (Tregs), myeloid-derived dendritic cells (MDSCs) and tumor associated macrophages (TAM), which can enhance survival of cancer cells directly or via the regulation of the tumor stroma...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29262348/cellular-differentiation-of-human-monocytes-is-regulated-by-time-dependent-interleukin-4-signaling-and-the-transcriptional-regulator-ncor2
#18
Jil Sander, Susanne V Schmidt, Branko Cirovic, Naomi McGovern, Olympia Papantonopoulou, Anna-Lena Hardt, Anna C Aschenbrenner, Christoph Kreer, Thomas Quast, Alexander M Xu, Lisa M Schmidleithner, Heidi Theis, Lan Do Thi Huong, Hermi Rizal Bin Sumatoh, Mario A R Lauterbach, Jonas Schulte-Schrepping, Patrick Günther, Jia Xue, Kevin Baßler, Thomas Ulas, Kathrin Klee, Natalie Katzmarski, Stefanie Herresthal, Wolfgang Krebs, Bianca Martin, Eicke Latz, Kristian Händler, Michael Kraut, Waldemar Kolanus, Marc Beyer, Christine S Falk, Bettina Wiegmann, Sven Burgdorf, Nicholas A Melosh, Evan W Newell, Florent Ginhoux, Andreas Schlitzer, Joachim L Schultze
Human in vitro generated monocyte-derived dendritic cells (moDCs) and macrophages are used clinically, e.g., to induce immunity against cancer. However, their physiological counterparts, ontogeny, transcriptional regulation, and heterogeneity remains largely unknown, hampering their clinical use. High-dimensional techniques were used to elucidate transcriptional, phenotypic, and functional differences between human in vivo and in vitro generated mononuclear phagocytes to facilitate their full potential in the clinic...
December 19, 2017: Immunity
https://www.readbyqxmd.com/read/29261410/cross-talk-between-radiation-and-immunotherapy-the-twain-shall-meet
#19
Swaminathan P Iyer, Clayton R Hunt, Tej K Pandita
There has been increased interest in the immune stimulatory properties of ionizing radiation based on several preclinical models and recently completed clinical studies performed in combination with checkpoint inhibitors. This is a paradigm shift in that it considers the role of radiation beyond its direct cytotoxic effects, however, the factors that promote or limit radiation-induced immunogenicity are still unclear. Here we review the role of radiation in modulating the various aspects of the tumor immune microenvironment and discuss in particular the direct effects of radiation on the DNA damage response and its immediate consequences to neighboring cells...
December 20, 2017: Radiation Research
https://www.readbyqxmd.com/read/29259715/clinical-trials-using-mesenchymal-stem-cells-in-liver-diseases-and-inflammatory-bowel-diseases
#20
REVIEW
Atsunori Tsuchiya, Yuichi Kojima, Shunzo Ikarashi, Satoshi Seino, Yusuke Watanabe, Yuzo Kawata, Shuji Terai
Mesenchymal stem cell (MSC) therapies have been used in clinical trials in various fields. These cells are easily expanded, show low immunogenicity, can be acquired from medical waste, and have multiple functions, suggesting their potential applications in a variety of diseases, including liver disease and inflammatory bowel disease. MSCs help prepare the microenvironment, in response to inflammatory cytokines, by producing immunoregulatory factors that modulate the progression of inflammation by affecting dendritic cells, B cells, T cells, and macrophages...
2017: Inflammation and Regeneration
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