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Dendritic cell immunotherapy

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https://www.readbyqxmd.com/read/27926855/temporally-programmed-cd8%C3%AE-dc-activation-enhances-combination-cancer-immunotherapy
#1
Alice Tzeng, Monique J Kauke, Eric F Zhu, Kelly D Moynihan, Cary F Opel, Nicole J Yang, Naveen Mehta, Ryan L Kelly, Gregory L Szeto, Willem W Overwijk, Darrell J Irvine, K Dane Wittrup
Numerous synergistic cancer immunotherapy combinations have been identified, but the effects of relative dose timing are rarely considered. In established syngeneic mouse tumor models, we found that staggering interferon-α (IFNα) administration after, rather than before or simultaneously with, serum-persistent interleukin-2 (IL-2) and tumor-specific antibody significantly increased long-term survival. Successful combination therapy required IFNα-induced activation of cross-presenting CD8α(+) dendritic cells (DCs) following the release of antigenic tumor debris by the IL-2- and antibody-mediated immune response...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27922697/regulation-of-pd-l1-expression-in-a-high-grade-invasive-human-oral-squamous-cell-carcinoma-microenvironment
#2
Mariko Hirai, Hiroko Kitahara, Yutaka Kobayashi, Koroku Kato, George Bou-Gharios, Hiroyuki Nakamura, Shuichi Kawashiri
Blockade of the programmed-death 1 receptor (PD-1)/programmed-death ligand (PD-L1) pathway efficiently reduces tumour growth and improves survival. Durable tumour regression with blockade of the PD-1/PD-L1 checkpoint has been demonstrated in recent clinical studies. Oral squamous cell carcinoma (OSCC) is highly immunosuppressive, and PD-L1 expression has been proposed as a potential mechanism responsible for this phenotype. Despite the fact that anti-PD-1 treatment can produce durable responses, such therapy appears to benefit only a subset of patients...
December 2, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#3
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911948/tlr3-induced-maturation-of-murine-dendritic-cells-regulates-ctl-responses-by-modulating-pd-l1-trafficking
#4
Aditi Varthaman, Hélène D Moreau, Mathieu Maurin, Philippe Benaroch
Targeting TLR3 through formulations of polyI:C is widely studied as an adjuvant in cancer immunotherapy. The efficacy of such targeting has been shown to increase in combination with anti-PD-L1 treatment. Nevertheless, the mechanistic details of the effect of polyI:C on DC maturation and the impact on T-DC interactions upon PD-L1 blockade is largely unknown. Here we found that although DC treatment with polyI:C induced a potent inflammatory response including the production of type I interferon, polyI:C treatment of DCs impaired activation of peptide specific CD8+ T cells mainly due to PD-L1...
2016: PloS One
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#5
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27906162/activation-of-myeloid-and-endothelial-cells-by-cd40l-gene-therapy-supports-t-cell-expansion-and-migration-into-the-tumor-microenvironment
#6
E Eriksson, R Moreno, I Milenova, L Liljenfeldt, L C Dieterich, L Christiansson, H Karlsson, G Ullenhag, S Mangsbo, A Dimberg, R Alemany, A Loskog
CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate Th1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27904768/combined-vegfr-and-ctla-4-blockade-increases-the-antigen-presenting-function-of-intratumoral-dcs-and-reduces-the-suppressive-capacity-of-intratumoral-mdscs
#7
Stephanie Du Four, Sarah K Maenhout, Simone P Niclou, Kris Thielemans, Bart Neyns, Joeri L Aerts
Melanoma brain metastases (MBM) occur in 10% to 50% of melanoma patients. They are often associated with a high morbidity and despite the improvements in the treatment of advanced melanoma, including immunotherapy, patients with MBM still have a poor prognosis. Antiangiogenic treatment was shown to reduce the immunosuppressive tumor microenvironment. Therefore we investigated the effect of the combination of VEGFR- and CTLA-4 blockade on the immune cells within the tumor microenvironment. In this study we investigated the effect of the combination of axitinib, a TKI against VEGFR-1, -2 and -3, with therapeutic inhibition of CTLA-4 in subcutaneous and intracranial mouse melanoma models...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903432/antigen-presentation-for-priming-t-cells-in-central-system
#8
Shaoni Dasgupta, Subhajit Dasgupta
Generation of myelin antigen-specific T cells is a major event in neuroimmune responses that causes demyelination. The antigen-priming of T cells and its location is important in chronic and acute inflammation. In autoimmune multiple sclerosis, the effector T cells are considered to generate in periphery. However, the reasons for chronic relapsing-remitting events are obscure. Considering mechanisms, a feasible aim of research is to investigate the role of antigen-primed T cells in lupus cerebritis. Last thirty years of investigations emphasize the relevance of microglia and infiltrated dendritic cells/macrophages as antigen presenting cells in the central nervous system...
November 27, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27898045/dendritic-cell-based-immunotherapies-to-fight-hiv-how-far-from-a-success-story-a-systematic-review-and-meta-analysis
#9
REVIEW
Antonio Victor Campos Coelho, Ronald Rodrigues de Moura, Anselmo Jiro Kamada, Ronaldo Celerino da Silva, Rafael Lima Guimarães, Lucas André Cavalcanti Brandão, Luiz Cláudio Arraes de Alencar, Sergio Crovella
The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports...
November 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27896368/targeting-of-the-wt191-138-fragment-to-human-dendritic-cells-improves-leukemia-specific-t-cell-responses-providing-an-alternative-approach-to-wt1-based-vaccination
#10
Nergui Dagvadorj, Anne Deuretzbacher, Daniela Weisenberger, Elke Baumeister, Johannes Trebing, Isabell Lang, Carolin Köchel, Markus Kapp, Kerstin Kapp, Andreas Beilhack, Thomas Hünig, Hermann Einsele, Harald Wajant, Götz Ulrich Grigoleit
Due to its immunogenicity and overexpression concomitant with leukemia progression, Wilms tumor protein 1 (WT1) is of particular interest for immunotherapy of AML relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, WT1-specific T-cell responses have mainly been induced by vaccination with peptides presented by certain HLA alleles. However, this approach is still not widely applicable in clinical practice due to common limitations of HLA restriction. Dendritic cell (DC) vaccines electroporated with mRNA encoding full-length protein have also been tested for generating WT1-derived peptides for presentation to T-cells...
November 28, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27877052/dendritic-cell-immunotherapy-versus-bevacizumab-plus-irinotecan-in-recurrent-malignant-glioma-patients-a-survival-gain-analysis
#11
Stefan-Alexandru Artene, Adina Turcu-Stiolica, Richard Hartley, Marius Eugen Ciurea, Oana Daianu, Corina Brindusa, Oana Alexandru, Ligia Gabriela Tataranu, Stefana Oana Purcaru, Anica Dricu
BACKGROUND: The bevacizumab and irinotecan protocol is considered a standard treatment regimen for recurrent malignant glioma. Recent advances in immunotherapy have hinted that vaccination with dendritic cells could become an alternative salvage therapy for the treatment of recurrent malignant glioma. METHODS: A search was performed on PubMed, Cochrane Library, Web of Science, ScienceDirect, and Embase in order to identify studies with patients receiving bevacizumab plus irinotecan or dendritic cell therapy for recurrent malignant gliomas...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27875974/nanoparticle-systems-modulating-myeloid-derived-suppressor-cells-for-cancer-immunotherapy
#12
Avia Wilkerson, Julian Kim, Alex Y Huang, Mei Zhang
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are preferentially expanded in cancer. They arise from myeloid progenitor cells that do not differentiate into mature dendritic cells (DCs), granulocytes, or macrophages, and are rather thought to play a pivotal role in immune escape and cancer progression. MDSCs are characterized by the ability to suppress T cell proliferation and cytotoxicity, inhibit natural killer T (NKT) cell activation, and induce the differentiation and expansion of regulatory T cells (Treg)...
November 22, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27875627/immunotherapy-approaches-in-the-treatment-of-malignant-brain-tumors
#13
REVIEW
Anastasie M Dunn-Pirio, Gordana Vlahovic
Glioblastoma is the most common malignant primary brain tumor. Despite standard-of-care treatment, consisting of maximal surgical resection followed by chemoradiation, both morbidity and mortality associated with this disease remain very poor. Therefore, there is an urgent need for more efficacious and well tolerated therapies. Advancing knowledge of the intricate interplay between malignant gliomas and the immune system, coupled with the recent launch of immunotherapy research for other cancers, has led to a veritable increase in immunotherapy investigation for glioblastoma and other malignant gliomas...
November 22, 2016: Cancer
https://www.readbyqxmd.com/read/27870103/role-of-immunotherapy-in-targeting-the-bone-marrow-microenvironment-in-multiple-myeloma-an-evolving-therapeutic-strategy
#14
Clement Chung
Multiple myeloma (referred to henceforth as myeloma) is a B-cell malignancy characterized by unregulated growth of plasma cells in the bone marrow. The treatment paradigm for myeloma underwent significant evolution in the last decade, with an improved understanding of the pathogenesis of the disease as well as the development of therapeutic agents that target not only the tumor cells but also their microenvironment. Despite these therapeutic advances, the prognosis of patients with relapsed or refractory myeloma remains poor...
November 21, 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27864613/oncolysate-loaded-escherichia-coli-bacterial-ghosts-enhance-the-stimulatory-capacity-of-human-dendritic-cells
#15
Jaroslav Michalek, Renata Hezova, Pavlina Turanek-Knötigova, Jana Gabkova, Marius Strioga, Werner Lubitz, Pavol Kudela
The natural adjuvant properties of bacterial ghosts (BGs) lie within the presence of intact pathogen-associated molecular patterns on their surface. BGs can improve the direct delivery, natural processing and presentation of target antigens within dendritic cells (DCs). Moreover, sensitization of human DCs by cancer cell lysate (oncolysate)-loaded BGs in the presence of IFN-α and GM-CSF enhanced DC maturation as indicated by an increased expression of maturation markers and co-stimulatory molecules, higher production of IL-12p70 and stimulation of significantly increased proliferation of both autologous CD4(+) and CD8(+) T cells compared to DCs matured in the presence of purified lipopolysaccharide...
November 18, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27864474/complement-component-3-regulates-ifn-%C3%AE-production-by-plasmacytoid-dendritic-cells-following-tlr7-activation-by-a-plant-virus-like-nanoparticle
#16
Marie-Ève Lebel, Marie-Pierre Langlois, Jean-François Daudelin, Esther Tarrab, Pierre Savard, Denis Leclerc, Alain Lamarre
The increasing use of plant viruses for the development of new vaccines and immunotherapy approaches poses questions regarding the mechanism by which the mammalian immune system recognizes these viruses. For example, although natural Abs (NA) and complement are key components of the innate immune system involved in the opsonization, phagocytosis, and destruction of microorganisms infecting mammals, their implication in plant virus recognition and immunogenicity is not well defined. In this study, we address the involvement of NA and the complement system in the activation of innate immunity through engagement of TLR7 with papaya mosaic virus (PapMV)-like nanoparticles...
November 18, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27864016/generation-of-antigen-specific-cytotoxic-t-lymphocytes-with-activated-b-cells
#17
Sun Ok Yun, Hee Young Shin, Chang-Yuil Kang, Hyoung Jin Kang
BACKGROUND AIMS: Dendritic cells are well known as the most potent antigen-presenting cells. Nonetheless, their use in immunotherapy has been limited by the time-consuming and laborious steps involved in their generation in vitro. Therefore, much attention has been placed on alternative antigen-presenting cells that are relatively more convenient to manipulate. METHODS: In this study, the efficacy of B cells as antigen-presenting cells, compared with dendritic cells, in the induction of cytotoxic T lymphocytes against cytomegalovirus-specific antigens was evaluated...
November 15, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27863552/generation-of-potent-porcine-monocyte-derived-dendritic-cells-modcs-by-modified-culture-protocol
#18
Teerawut Nedumpun, Patcharee Ritprajak, Sanipa Suradhat
In vitro derivation of dendritic cells (DCs) is an alternative approach to overcome the low frequency of primary DCs and the difficulty of isolation techniques for studying DC immunobiology. To date, the conventional culture protocol of porcine monocyte-derived DCs (MoDCs) has been widely used. However, this protocol is not practical due to the requirement of a substantial number of blood monocytes, and the process often interferes with DC maturation. To improve in vitro porcine MoDC generation, we modified the previous conventional DC generation protocol, based on the human and mouse primary DC culture system, and compared phenotypic and functional features of MoDCs derived from the modified protocol to the conventional protocol...
December 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27861999/forkhead-box-protein-3-foxp3-producing-dendritic-cells-suppress-allergic-response
#19
Xiao-Yu Liu, Ling-Zhi Xu, Xiang-Qian Luo, Xiao-Rui Geng, Zhi-Qiang Liu, Li-Teng Yang, Gui Yang, Si Chen, Zhi-Gang Liu, Hua-Bin Li, Li-Tao Yang, Tian-Gang Luan, Ping-Chang Yang
BACKGROUND: The generation of the tolerogenic dendritic cells (DC) is not fully understood yet. Forkhead box protein-3 (Foxp3) is an important molecule in the immune tolerance. This study tests a hypothesis that DCs express Foxp3, which can be up regulated by Staphylococcal enterotoxin B (SEB). METHODS: The expression of Foxp3 by DCs was evaluated by real time RT-PCR, Western blotting, flow cytometry and chromatin immunoprecipitation assay. RESULTS: We observed that mice treated with SEB at 0...
November 15, 2016: Allergy
https://www.readbyqxmd.com/read/27855783/long-term-intravital-imaging-of-the-multicolor-coded-tumor-microenvironment-during-combination-immunotherapy
#20
Shuhong Qi, Hui Li, Lisen Lu, Zhongyang Qi, Lei Liu, Lu Chen, Guanxin Shen, Ling Fu, Qingming Luo, Zhihong Zhang
The combined-immunotherapy of adoptive cell therapy (ACT) and cyclophosphamide (CTX) is one of the most efficient treatments for melanoma patients. However, synergistic effects of CTX and ACT on the spatio-temporal dynamics of immunocytes in vivo have not been described. Here, we visualized key cell events of immunotherapy-elicited immunoreactions in a multicolor-coded tumor microenvironment, and then established an optimal strategy of metronomic combined-immunotherapy to enhance anti-tumor efficacy. Intravital imaging data indicated that regulatory T cells formed an 'immunosuppressive ring' around a solid tumor...
November 18, 2016: ELife
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