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Dendritic cell immunotherapy

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https://www.readbyqxmd.com/read/28088784/a-phase-i-clinical-study-of-autologous-dendritic-cell-therapy-in-patients-with-relapsed-or-refractory-multiple-myeloma
#1
Sung-Hoon Jung, Hyun-Ju Lee, Youn-Kyung Lee, Deok-Hwan Yang, Hyeoung-Joon Kim, Joon Haeng Rhee, Frank Emmrich, Je-Jung Lee
Cellular immunotherapy is emerging as a potential immunotherapeutic modality in multiple myeloma (MM). We have developed potent immunotherapeutic agent (VAX-DC/MM) generated by dendritic cells (DCs) loaded with autologous myeloma cells irradiated with ultraviolet B. In this study, we evaluated the safety and efficacy of VAX-DC/MM in patients with relapsed or refractory MM. This trial enrolled relapsed or refractory MM patients who had received both thalidomide- and bortezomib-based therapies. Patients received the intradermal VAX-DC/MM injection every week for 4 weeks...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088065/methionine-enkephalin-menk-mounts-antitumor-effect-via-regulating-dendritic-cells-dcs
#2
Yiming Meng, Xinghua Gao, Wenna Chen, Nicolas P Plotnikoff, Noreen Griffin, Guirong Zhang, Fengping Shan
MENK, an endogenous opioid peptide has been reported to have many immunological and antitumor activities. So far the detailed mechanisms of antitumor through regulating DCs by MENK have not been elucidated yet. The aim of this work was to investigate the antitumor mechanisms of MENK via regulating DC. The monitoring methods, such as ELISA, MTS assay, CFSE, Real-time PCR and Western blot were included in our research. We found bone marrow derived dendritic cells (BMDCs) in 36 female C57BL/6 mice treated with MENK enhanced expression of key surface molecules, increased production of critical cytokines reduced endocytosis of FITC-dextran, upregulated TLR4 through MyD88/NF-κB signaling pathway and mounted higher antitumor activity...
January 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28079009/emerging-roles-of-calreticulin-in-cancer-implications-for-therapy
#3
Kavya Venkateswaran, Amit Verma, Anant Narayan Bhatt, Anju Shrivastava, Kailash Manda, Hanumantharao G Raj, Ashok Prasad, Christophe Len, Virinder S Parmar, Bilikere Dwarakanath
Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies...
January 11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28069499/precise-manipulation-of-biophysical-particle-parameters-enables-control-of-proinflammatory-cytokine-production-in-presence-of-tlr-3-and-4-ligands
#4
Yoshinori Kakizawa, Jung Seok Lee, Brendan Bell, Tarek M Fahmy
: The biophysical parameters governing nanoparticle (NP)-cell interactions significantly affect biological responses, particularly in the application of NP-based immunotherapeutics. Modulation of the surface biophysical character of NPs can be achieved via introduction of amino acids, which offer the ability to fine tune a range of biophysical parameters of interest. We employed this approach using monodisperse silica NPs coated with numerous poly(amino acid)s (PAAs). The NPs were incubated with dendritic cells (DCs) in conjunction with TLR ligands and production of IL-1β from DCs and IFNγ from T cells primed by these DCs were measured...
January 6, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28065340/enhancing-allergen-presentation-platforms-for-sublingual-immunotherapy
#5
REVIEW
P Moingeon, V Lombardi, V Baron-Bodo, L Mascarell
Sublingual immunotherapy (SLIT) relies on high doses of allergens to treat patients with type I allergies. Although SLIT is commonly performed without any adjuvant or delivery system, allergen(s) could be further formulated with allergen-presentation platforms to better target oral dendritic cells eliciting regulatory immune responses. Improving the availability of allergens to the immune system should enhance SLIT efficacy, while allowing to decrease allergen dosing. Herein, we present an overview of adjuvants and vector systems that have been, or could be, considered as candidate allergen-presentation platforms for the sublingual route...
January 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28060726/immunogenic-cancer-cell-death-selectively-induced-by-near-infrared-photoimmunotherapy-initiates-host-tumor-immunity
#6
Mikako Ogawa, Yusuke Tomita, Yuko Nakamura, Min-Jung Lee, Sunmin Lee, Saori Tomita, Tadanobu Nagaya, Kazuhide Sato, Toyohiko Yamauchi, Hidenao Iwai, Abhishek Kumar, Timothy Haystead, Hari Shroff, Peter L Choyke, Jane B Trepel, Hisataka Kobayashi
Immunogenic cell death (ICD) is a form of cell death that activates an adaptive immune response against dead-cell-associated antigens. Cancer cells killed via ICD can elicit antitumor immunity. ICD is efficiently induced by near-infrared photo-immunotherapy (NIR-PIT) that selectively kills target-cells on which antibody-photoabsorber conjugates bind and are activated by NIR light exposure. Advanced live cell microscopies showed that NIR-PIT caused rapid and irreversible damage to the cell membrane function leading to swelling and bursting, releasing intracellular components due to the influx of water into the cell...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28052994/local-delivery-of-the-tlr9-ligand-cpg-down-regulates-host-immune-and-inflammatory-responses-ameliorating-established-leishmania-viannia-panamensis-chronic-infection
#7
Allison K Ehrlich, Olga L Fernández, Daniel Rodriguez-Pinto, Tiago M Castilho, Maria J Corral Caridad, Karen Goldsmith-Pestana, Nancy Gore Saravia, Diane McMahon-Pratt
Infection by Leishmania (Viannia) panamensis, the predominant etiologic agent for cutaneous leishmaniasis in Colombia, is characterized by a chronic mixed-inflammatory response. Current treatment options are plagued by toxicity, lengthy treatment regimens and growing evidence of drug resistance. Immunotherapy, modulating the immune system to mount a protective response, may provide an alternate therapeutic approach. We investigated the ability of the TLR9 ligand, CpG, to modulate established disease in the L...
January 4, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28052512/innate-immunity-in-cutaneous-melanoma
#8
REVIEW
C Mignogna, E Scali, C Camastra, I Presta, P Zeppa, T Barni, G Donato, U Bottoni, A Di Vito
The skin immune system is composed of a vast network of immune cells, including lymphocytes, macrophages, neutrophils, dendritic cells and Langerhans cells, which not only are involved in inflammatory responses but also contribute to homeostatic function and may participate in the various steps of carcinogenesis. Many studies support the notion that innate immunity has a key role in the development, growth and prognosis of cutaneous malignant melanoma (MM), through the release of pro- and/or anti-inflammatory cytokines and tumour growth factors...
January 4, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28052005/bortezomib-augments-lymphocyte-stimulatory-cytokine-signaling-in-the-tumor-microenvironment-to-sustain-cd8-t-cell-antitumor-function
#9
Samuel T Pellom, Duafalia F Dudimah, Menaka C Thounaojam, Roman V Uzhachenko, Ashutosh Singhal, Ann Richmond, Anil Shanker
Tumor-induced immune tolerance poses a major challenge for therapeutic interventions aimed to manage cancer. We explored approaches to overcome T-cell suppression in murine breast and kidney adenocarcinomas, and lung fibrosarcoma expressing immunogenic antigens. We observed that treatment with a reversible proteasome inhibitor bortezomib (1 mg/kg body weight) in tumor-bearing mice significantly enhanced the expression of lymphocyte-stimulatory cytokines IL-2, IL-12, and IL-15. Notably, bortezomib administration reduced pulmonary nodules of mammary adenocarcinoma 4T1...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28038471/prognostic-impact-of-immune-microenvironment-in-laryngeal-and-pharyngeal-squamous-cell-carcinoma-immune-cell-subtypes-immuno-suppressive-pathways-and-clinicopathologic-characteristics
#10
Georgia Karpathiou, Francois Casteillo, Jean-Baptiste Giroult, Fabien Forest, Pierre Fournel, Alessandra Monaya, Marios Froudarakis, Jean Marc Dumollard, Jean Michel Prades, Michel Peoc'h
BACKGROUND: Immune system affects prognosis of various malignancies. Anti-immune pathways like PD-L1 and CTLA4 are used by the tumor to overcome immune system and they serve as immunotherapy targets. The immune microenvironment of head-and-neck squamous cell carcinoma (SCCHN) has not been sufficiently studied. PATIENTS AND METHODS: 152 SCCHN were immunohistochemically studied for the expression of CD3, CD8, CD57, CD4, granzyme b, CD20, CD163, S100, PD-L1, CTLA4 and CXCR4...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032353/allergooncology-the-impact-of-allergy-in-oncology-eaaci-position-paper
#11
E Jensen-Jarolim, H J Bax, R Bianchini, M Capron, C Corrigan, M Castells, D Dombrowicz, T R Daniels-Wells, J Fazekas, E Fiebiger, S Gatault, H J Gould, J Janda, D H Josephs, P Karagiannis, F Levi-Schaffer, A Meshcheryakova, D Mechtcheriakova, Y Mekori, F Mungenast, E A Nigro, M L Penichet, F Redegeld, L Saul, J Singer, J F Spicer, A G Siccardi, E Spillner, M C Turner, E Untersmayr, L Vangelista, S N Karagiannis
Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both anti-tumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments...
December 29, 2016: Allergy
https://www.readbyqxmd.com/read/28028922/n-dihydrogalactochitosan-as-a-potent-immune-activator-for-dendritic-cells
#12
Ahmed El-Hussein, Samuel S K Lam, Joseph Raker, Wei R Chen, Michael R Hamblin
Immunotherapy has become one of the fastest growing areas of cancer research. A promising in situ autologous cancer vaccine (inCVAX) uses a novel immune activator, N-dihydrogalactochitosan (GC), that possesses the ability to stimulate dendritic cells (DC). inCVAX is a combination treatment procedure involving treatment of the tumor with a thermal near-infrared laser to liberate whole cell tumor antigens, followed by injection of GC (a glucosamine polymer with galactose attached to the amino groups) into the treated tumor thereby inducing a systemic anti-tumor immune response...
December 28, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28027502/bioactive-polysaccharide-based-ph-sensitive-polymers-for-cytoplasmic-delivery-of-antigen-and-activation-of-antigen-specific-immunity
#13
Eiji Yuba, Ayaka Yamaguchi, Yuta Yoshizaki, Atsushi Harada, Kenji Kono
For establishment of cancer immunotherapy, antigen carriers are needed which have functions not only to deliver antigen into cytosol of dendritic cells (DCs), which induces antigen-specific cellular immune responses, but also to activate DCs. We previously reported cytoplasmic delivery of antigen using liposomes modified with pH-sensitive polymers such as carboxylated poly(glycidol)s or dextran. Modification using these polymers provides stable liposomes with pH-sensitive fusogenic/membrane-disruptive ability...
December 22, 2016: Biomaterials
https://www.readbyqxmd.com/read/28025976/dendritic-cell-based-immunotherapy
#14
REVIEW
Rachel L Sabado, Sreekumar Balan, Nina Bhardwaj
Immunotherapy using dendritic cell (DC)-based vaccination is an approved approach for harnessing the potential of a patient's own immune system to eliminate tumor cells in metastatic hormone-refractory cancer. Overall, although many DC vaccines have been tested in the clinic and proven to be immunogenic, and in some cases associated with clinical outcome, there remains no consensus on how to manufacture DC vaccines. In this review we will discuss what has been learned thus far about human DC biology from clinical studies, and how current approaches to apply DC vaccines in the clinic could be improved to enhance anti-tumor immunity...
January 2017: Cell Research
https://www.readbyqxmd.com/read/28024156/designer-vaccine-nanodiscs-for-personalized-cancer-immunotherapy
#15
Rui Kuai, Lukasz J Ochyl, Keith S Bahjat, Anna Schwendeman, James J Moon
Despite the tremendous potential of peptide-based cancer vaccines, their efficacy has been limited in humans. Recent innovations in tumour exome sequencing have signalled the new era of personalized immunotherapy with patient-specific neoantigens, but a general methodology for stimulating strong CD8α(+) cytotoxic T-lymphocyte (CTL) responses remains lacking. Here we demonstrate that high-density lipoprotein-mimicking nanodiscs coupled with antigen (Ag) peptides and adjuvants can markedly improve Ag/adjuvant co-delivery to lymphoid organs and sustain Ag presentation on dendritic cells...
December 26, 2016: Nature Materials
https://www.readbyqxmd.com/read/28018989/the-intersection-of-radiotherapy-and-immunotherapy-mechanisms-and-clinical-implications
#16
Michael Spiotto, Yang-Xin Fu, Ralph R Weichselbaum
By inducing DNA damage, radiotherapy both reduces tumor burden and enhances anti-tumor immunity. Here, we will review the mechanisms by which radiation induces anti-tumor immune responses that can be augmented using immunotherapies to facilitate tumor regression. Radiotherapy increases inflammation in tumors by activating the NF-κB and the Type I interferon response pathways to induce expression of pro-inflammatory cytokines. This inflammation coupled with antigen release from irradiated cells facilitates dendritic cell maturation and cross-presentation of tumor antigens to prime tumor-specific T cell responses...
September 2016: Science Immunology
https://www.readbyqxmd.com/read/28018602/fusion-of-the-dendritic-cell-targeting-chemokine-mip3%C3%AE-to-melanoma-antigen-gp100-in-a-therapeutic-dna-vaccine-significantly-enhances-immunogenicity-and-survival-in-a-mouse-melanoma-model
#17
James T Gordy, Kun Luo, Hong Zhang, Arya Biragyn, Richard B Markham
BACKGROUND: Although therapeutic cancer vaccines have been mostly disappointing in the clinic, the advent of novel immunotherapies and the future promise of neoantigen-based therapies have created the need for new vaccine modalities that can easily adapt to current and future developments in cancer immunotherapy. One such novel platform is a DNA vaccine fusing the chemokine Macrophage Inflammatory Protein-3α (MIP-3α) to an antigen, here melanoma antigen gp100. Previous published work has indicated that MIP-3α targets nascent peptides to immature dendritic cells, leading to processing by class I and II MHC pathways...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28011934/exogenous-il-33-restores-dendritic-cell-activation-and-maturation-in-established-cancer
#18
Donye Dominguez, Cong Ye, Zhe Geng, Siqi Chen, Jie Fan, Lei Qin, Alan Long, Long Wang, Zhuoli Zhang, Yi Zhang, Deyu Fang, Timothy M Kuzel, Bin Zhang
The role of IL-33, particularly in tumor growth and tumor immunity, remains ill-defined. We show that exogenous IL-33 can induce robust antitumor effect through a CD8(+) T cell-dependent mechanism. Systemic administration of rIL-33 alone was sufficient to inhibit growth of established tumors in transplant and de novo melanoma tumorigenesis models. Notably, in addition to a direct action on CD8(+) T cell expansion and IFN-γ production, rIL-33 therapy activated myeloid dendritic cells (mDCs) in tumor-bearing mice, restored antitumor T cell activity, and increased Ag cross-presentation within the tumor microenvironment...
December 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28011931/htlv-1-tax-specific-ctl-epitope-pulsed-dendritic-cell-therapy-reduces-proviral-load-in-infected-rats-with-immune-tolerance-against-tax
#19
Satomi Ando, Atsuhiko Hasegawa, Yuji Murakami, Na Zeng, Natsuko Takatsuka, Yasuhiro Maeda, Takao Masuda, Youko Suehiro, Mari Kannagi
Adult T cell leukemia/lymphoma (ATL), a CD4(+) T cell malignancy with a poor prognosis, is caused by human T cell leukemia virus type 1 (HTLV-1) infection. High proviral load (PVL) is a risk factor for the progression to ATL. We previously reported that some asymptomatic carriers had severely reduced functions of CTLs against HTLV-1 Tax, the major target Ag. Furthermore, the CTL responses tended to be inversely correlated with PVL, suggesting that weak HTLV-1-specific CTL responses may be involved in the elevation of PVL...
December 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28008905/the-tumour-microenvironment-harbours-ontogenically-distinct-dendritic-cell-populations-with-opposing-effects-on-tumour-immunity
#20
Damya Laoui, Jiri Keirsse, Yannick Morias, Eva Van Overmeire, Xenia Geeraerts, Yvon Elkrim, Mate Kiss, Evangelia Bolli, Qods Lahmar, Dorine Sichien, Jens Serneels, Charlotte L Scott, Louis Boon, Patrick De Baetselier, Massimiliano Mazzone, Martin Guilliams, Jo A Van Ginderachter
Various steady state and inflamed tissues have been shown to contain a heterogeneous DC population consisting of developmentally distinct subsets, including cDC1s, cDC2s and monocyte-derived DCs, displaying differential functional specializations. The identification of functionally distinct tumour-associated DC (TADC) subpopulations could prove essential for the understanding of basic TADC biology and for envisaging targeted immunotherapies. We demonstrate that multiple mouse tumours as well as human tumours harbour ontogenically discrete TADC subsets...
December 23, 2016: Nature Communications
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