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Dendritic cell immunotherapy

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https://www.readbyqxmd.com/read/28811970/trial-watch-dendritic-cell-based-anticancer-immunotherapy
#1
REVIEW
Abhishek D Garg, Monica Vara Perez, Marco Schaaf, Patrizia Agostinis, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Dendritic cell (DC)-based vaccines against cancer have been extensively developed over the past two decades. Typically DC-based cancer immunotherapy entails loading patient-derived DCs with an appropriate source of tumor-associated antigens (TAAs) and efficient DC stimulation through a so-called "maturation cocktail" (typically a combination of pro-inflammatory cytokines and Toll-like receptor agonists), followed by DC reintroduction into patients. DC vaccines have been documented to (re)activate tumor-specific T cells in both preclinical and clinical settings...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811965/adjuvant-immunotherapy-with-autologous-dendritic-cells-for-hepatocellular-carcinoma-randomized-phase-ii-study
#2
Jeong-Hoon Lee, Won Young Tak, Yoon Lee, Min-Kyu Heo, Jae-Sung Song, Hak-Yeop Kim, Soo Young Park, Si Hyun Bae, Joon Hyeok Lee, Jeong Heo, Ki-Hwan Kim, Yong-Soo Bae, Yoon Jun Kim
Our previous phase I/IIA study showed that autologous dendritic cells (DCs) pulsed with tumor-associated antigens are well tolerated in patients with hepatocellular carcinoma (HCC). In this randomized, multicenter, open-label, phase II trial, we investigated the efficacy and safety of this DC-based adjuvant immunotherapy with 156 patients, who treated for HCC with no evidence of residual tumor after standard treatment modalities. Patients were randomly assigned to immunotherapy (n = 77; injection of 3 × 10(7) DC cells, six times over 14 weeks) or control (n = 79; no treatment)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811960/rehmannia-glutinosa-polysaccharide-induces-toll-like-receptor-4-dependent-spleen-dendritic-cell-maturation-and-anti-cancer-immunity
#3
Li Xu, Minseok Kwak, Wei Zhang, Ling Zeng, Peter Chang-Whan Lee, Jun-O Jin
Rehmannia glutinosa polysaccharide (RGP) has shown an activation of immune cells in vitro. However, the immune stimulatory effect of RGP in a mouse in vivo is not well studied. In this study, we examined the effect of RGP on dendritic cell (DC) activation and anticancer immunity in vivo. Treatments of RGP in C56BL/6 mice induced increased levels of co-stimulatory molecule expression and pro-inflammatory cytokine production in spleen DCs dependent on toll-like receptor 4 (TLR4), and those DCs promoted interferon-gamma (IFNγ) production in CD4(+) and CD8(+) T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811957/mapping-the-human-t-cell-repertoire-to-recurrent-driver-mutations-in-myd88-and-ezh2-in-lymphoma
#4
Julie S Nielsen, Andrew R Chang, Darin A Wick, Colin G Sedgwick, Zusheng Zong, Andrew J Mungall, Spencer D Martin, Natalie N Kinloch, Susann Ott-Langer, Zabrina L Brumme, Steven P Treon, Joseph M Connors, Randy D Gascoyne, John R Webb, Brian R Berry, Ryan D Morin, Nicol Macpherson, Brad H Nelson
Oncogenic "driver" mutations are theoretically attractive targets for the immunotherapy of lymphoid cancers, yet the proportion that can be recognized by T cells remains poorly defined. To address this issue without any confounding effects of the patient's immune system, we assessed T cells from 19 healthy donors for recognition of three common driver mutations in lymphoma: MYD88(L265P), EZH2(Y641F) , and EZH2(Y641N) . Donors collectively expressed the 10 most prevalent HLA class I alleles, including HLA-A*02:01...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28802126/derp1-modified-dendritic-cells-attenuate-allergic-inflammation-by-regulating-the-development-of-t-helper-type1-th1-th2-cells-and-regulatory-t-cells-in-a-murine-model-of-allergic-rhinitis
#5
Shaoqing Yu, Bing Han, Shuangxi Liu, Hong Wang, Wenjie Zhuang, Yu Huang, Ruxin Zhang
The CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are known to regulate Th2-induced allergic rhinitis (AR). In this study, we evaluated the efficacy of Derp1-modified dendritic cells (DCs) in AR immunotherapy. Derp1 was synthesized and transfected into DCs to generate Derp1-modified DCs. Phenotypes of Derp1-modified DCs were analyzed with flow cytometry using antibodies against DC markers CD11c, CD11b, CD59, CD103 and Toll-like receptor 1(TLR1). Four groups of subject mice were formed; the controls were treated with immature DCs, while the AR mice models were sensitized with Derp1(AR) and treated with DCs(DC-AR) or Derp1-modified DCs (Derp1DC-AR)...
August 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28790822/complement-c3-dependent-uptake-of-targeted-liposomes-into-human-macrophages-b-cells-dendritic-cells-neutrophils-and-mdscs
#6
Alexandra Francian, Kristine Mann, Max Kullberg
Antitumor immunity in cancer patients is heavily modulated by cells of the innate immune system. Antigen-presenting cells, including dendritic cells, macrophages, and B cells, initiate immune recognition of tumor antigen by displaying antigen to effector cells. Countering this immune stimulation are immunosuppressive cells which include M2 macrophages, N2 neutrophils, and myeloid-derived suppressor cells (MDSCs). To create effective cancer immunotherapies, it is critical that we can target these important cell types of the immune system with immunostimulatory compounds...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28780933/%C3%AE-%C3%AE-t-cells-unexpected-regulators-of-cancer-development-and-progression
#7
REVIEW
Christopher Fleming, Samantha Morrissey, Yihua Cai, Jun Yan
Accumulating evidence suggests a role for gamma delta (γδ) T cells as unexpected drivers of tumor development and progression. These protumoral γδ T cells are abundant in the tumor microenvironment in both mouse and human. They promote tumor progression by: (i) inducing an immunosuppressive tumor microenvironment and angiogenesis via cytokine production; (ii) functioning as regulatory T (Treg)/T helper 2 (Th2)-like cells; (iii) interfering with dendritic cell (DC) effector function; and (iv) inhibiting antitumor adaptive T cell immunity via the programmed death-1 (PD-1)-programmed death ligand-1 (PD-L1) pathway...
August 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28777336/development-of-ph-sensitive-dextran-derivatives-with-strong-adjuvant-function-and-their-application-to-antigen-delivery
#8
Eiji Yuba, Shinya Uesugi, Maiko Miyazaki, Yuna Kado, Atsushi Harada, Kenji Kono
To achieve efficient cancer immunotherapy, the induction of cytotoxic T lymphocyte-based cellular immunity is necessary. In order to induce cellular immunity, antigen carriers that can deliver antigen into cytosol of antigen presenting cells and can activate these cells are required. We previously developed 3-methyl glutarylated dextran (MGlu-Dex) for cytoplasmic delivery of antigen via membrane disruption ability at weakly acidic pH in endosome/lysosomes. MGlu-Dex-modified liposomes delivered model antigens into cytosol of dendritic cells and induced antigen-specific cellular immunity...
August 4, 2017: Membranes
https://www.readbyqxmd.com/read/28769554/the-modulation-of-enzyme-indoleamine-2-3-dioxygenase-from-dendritic-cells-for-the-treatment-of-type-1-diabetes-mellitus
#9
REVIEW
Débora Moitinho Abram, Luis Gustavo Romani Fernandes, Antônio Celso Saragossa Ramos Filho, Patrícia Ucelli Simioni
Diabetes mellitus type 1 (DM1) is an autoimmune disease in which β-cells of the pancreas islet are destroyed by T lymphocytes. Specific T cells are activated by antigen-presenting cells, mainly dendritic cells (DCs). It is already known that the regulation of tryptophan pathway in DC can be a mechanism of immunomodulation. The enzyme indoleamine 2,3-dioxygenase (IDO) is present in many cells, including DC, and participates in the metabolism of the amino acid tryptophan. Recent studies suggest the involvement of IDO in the modulation of immune response, which became more evident after the in vitro demonstration of IDO production by DC and of the ability of these cells to inhibit lymphocyte function through the control of tryptophan metabolism...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28765071/ficz-generates-human-tdcs-that-induce-cd4-cd25-high-foxp3-treg-like-cell-differentiation
#10
Brenda B Jurado-Manzano, Daniel Zavala-Reyes, Edgar A Turrubiartes-Martínez, Diana P Portales-Pérez, Roberto González-Amaro, Esther Layseca-Espinosa
Dendritic cells (DCs) play a central role in the maintenance of immune homeostasis, their participation as professional antigen presenting cells is essential to the initiation of the adaptive immune response as well as to the induction of tolerance. The recently described role of the aryl hydrocarbon receptor (AhR) in the immune system, particularly in the modulation of the adaptive immune response has attracted the attention as a potential player in the induction of immune tolerance. However, the effects of AhR activation through endogenous ligands on human DCs have been poorly evaluated...
July 29, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28763795/intratumoral-delivery-of-inactivated-modified-vaccinia-virus-ankara-imva-induces-systemic-antitumor-immunity-via-sting-and-batf3-dependent-dendritic-cells
#11
Peihong Dai, Weiyi Wang, Ning Yang, Cristian Serna-Tamayo, Jacob M Ricca, Dmitriy Zamarin, Stewart Shuman, Taha Merghoub, Jedd D Wolchok, Liang Deng
Advanced cancers remain a therapeutic challenge despite recent progress in targeted therapy and immunotherapy. Novel approaches are needed to alter the tumor immunosuppressive microenvironment and to facilitate the recognition of tumor antigens that leads to antitumor immunity. Poxviruses, such as modified vaccinia virus Ankara (MVA), have potential as immunotherapeutic agents. We show that infection of conventional dendritic cells (DCs) with heat- or ultraviolet-inactivated MVA leads to higher levels of interferon induction than MVA alone through the cGAS (cyclic guanosine monophosphate-adenosine monophosphate synthase)-STING cytosolic DNA-sensing pathway...
May 19, 2017: Science Immunology
https://www.readbyqxmd.com/read/28763794/targeting-latency-associated-peptide-promotes-antitumor-immunity
#12
Galina Gabriely, Andre P da Cunha, Rafael M Rezende, Brendan Kenyon, Asaf Madi, Tyler Vandeventer, Nathaniel Skillin, Stephen Rubino, Lucien Garo, Maria A Mazzola, Panagiota Kolypetri, Amanda J Lanser, Thais Moreira, Ana Maria C Faria, Hans Lassmann, Vijay Kuchroo, Gopal Murugaiyan, Howard L Weiner
Regulatory T cells (Tregs) promote cancer by suppressing antitumor immune responses. We found that anti-LAP antibody, which targets the latency-associated peptide (LAP)/transforming growth factor-β (TGF-β) complex on Tregs and other cells, enhances antitumor immune responses and reduces tumor growth in models of melanoma, colorectal carcinoma, and glioblastoma. Anti-LAP decreases LAP(+) Tregs, tolerogenic dendritic cells, and TGF-β secretion and is associated with CD8(+) T cell activation. Anti-LAP increases infiltration of tumors by cytotoxic CD8(+) T cells and reduces CD103(+) CD8 T cells in draining lymph nodes and the spleen...
May 19, 2017: Science Immunology
https://www.readbyqxmd.com/read/28763132/hydrolysed-ovalbumin-offers-more-effective-preventive-and-therapeutic-protection-against-egg-allergy-than-the-intact-protein
#13
D Lozano-Ojalvo, L Pérez-Rodríguez, A Pablos-Tanarro, E Molina, R López-Fandiño
BACKGROUND: The application of specific immunotherapy to stimulate oral tolerance towards food allergens is hampered by the high frequency of adverse side effects and the excessive duration of the treatments. OBJECTIVE: In this work, a hydrolysate of ovalbumin with pepsin (OP), selected for its low IgE reactivity and Th2-stimulating capacity, was assayed for its ability to prevent and treat allergy to egg white (EW). METHODS: As a first step, the safety of OP, in terms of the absence of sensitizing and eliciting potential, was evaluated in BALB/c mice...
August 1, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28763105/physiological-doses-of-red-light-induce-il-4-release-in-co-cultures-between-human-keratinocytes-and-immune-cells
#14
Cheryl Leong, Paul L Bigliardi, Gopu Sriram, Bijin Veonice Au, John Connolly, Mei Bigliardi-Qi
Phototherapy is routinely used for the treatment of various skin conditions and targeted therapy of superficial cancers. However, the molecular mechanisms behind their biological effects and the need for efficacy enhancing photosensitizers are not well addressed. Particularly, not much is known about the inherent effect of light from the visible spectrum on cytokine release and its downstream effects in keratinocytes and immune cells located in skin and therefore exposed to light. To address this, we delivered calibrated doses of well-defined light qualities (380 to 660 nm) to co-cultures of human keratinocytes and macrophage/dendritic cells in the absence or presence of the commonly used photosensitizer 8-methoxypsoralen (8-MOP)...
August 1, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28763099/autologous-tolerogenic-dendritic-cells-derived-from-monocytes-of-systemic-lupus-erythematosus-patients-and-healthy-donors-show-a-stable-and-immunosuppressive-phenotype
#15
Javiera Obreque, Fabián Vega, Andy Torres, Loreto Cuitino, Juan P Mackern-Oberti, Paola Viviani, Alexis Kalergis, Carolina Llanos
Systemic Lupus Erythematosus (SLE) is an autoimmune disease with unrestrained T-cell and B cell activity towards self-antigens. Evidence shows that apoptotic cells (ApoCells) trigger an autoreactive response against nuclear antigens in susceptible individuals. In this study, we focus on generating and characterizing tolerogenic dendritic cells (tolDCs) to restore tolerance to ApoCells. Monocyte-derived dendritic cells (DCs) from healthy controls (HC) and SLE patients were treated with dexamethasone (DEXA) and rosiglitazone (RGZ) to induce tolDCs...
August 1, 2017: Immunology
https://www.readbyqxmd.com/read/28760498/differences-and-similarities-between-sublingual-immunotherapy-of-allergy-and-oral-tolerance
#16
REVIEW
Philippe Moingeon, Laurent Mascarell
Allergen immunotherapy is the only treatment altering the natural course of IgE-mediated allergies. Whereas the subcutaneous route for immunotherapy (SCIT) has been historically considered as a reference, we discuss herein the relative advantages of the sublingual and oral routes as alternatives to SCIT in order to elicit allergen-specific tolerance. The buccal and gut immune systems are similarly organized to favor immune tolerance to antigens/allergens, due to the presence of tolerogenic dendritic cells and macrophages promoting the differentiation of CD4(+) regulatory T cells...
July 28, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28756740/c-type-lectin-receptor-s-targeted-nanoliposomes-an-intelligent-approach-for-effective-cancer-immunotherapy
#17
Rajeev Sharma, Nishi Mody, Varun Kushwah, Sanyog Jain, S P Vyas
AIM: The purpose of present approach is to target C-Type lectin (CTL) receptors for preferential uptake by the macrophages/dendritic cells and improving the cross-presentation of ovalbumin. MATERIALS & METHODS: Conventional and engineered nanoliposomes (MPNLs) were fabricated and extensively characterized. The nanoliposome(s) was spherical in shape; and their ζ potential, size and ovalbumin loading efficiency were recorded to be 268 ± 4.15 nm, 23.4 ± 0.35 mV, 46...
July 31, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28756536/therapeutic-blockade-of-foxp3-in-experimental-breast-cancer-models
#18
Mariela A Moreno Ayala, María Florencia Gottardo, Mercedes Imsen, Antonela S Asad, Elisa Bal de Kier Joffé, Noelia Casares, Juan José Lasarte, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Regulatory T cells (Tregs) impair the clinical benefit of cancer immunotherapy. To optimize the antitumor efficacy of therapeutic dendritic cell (DC) vaccines, we aimed to inhibit Foxp3, a transcription factor required for Treg function. METHODS: Mice bearing established syngeneic LM3 and 4T1 breast tumors were treated with antitumor DC vaccines and a synthetic peptide (P60) that has been shown to inhibit Foxp3. RESULTS: Treatment with P60 improved the therapeutic efficacy of DC vaccines in these experimental models...
July 29, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28754680/versican-derived-matrikines-regulate-batf3-dendritic-cell-differentiation-and-promote-t-cell-infiltration-in-colorectal-cancer
#19
Chelsea Hope, Philip B Emmerich, Athanasios Papadas, Adam Pagenkopf, Kristina A Matkowskyj, Dana R Van De Hey, Susan N Payne, Linda Clipson, Natalie S Callander, Peiman Hematti, Shigeki Miyamoto, Michael G Johnson, Dustin A Deming, Fotis Asimakopoulos
Colorectal cancer originates within immunologically complex microenvironments. To date, the benefits of immunotherapy have been modest, except in neoantigen-laden mismatch repair-deficient tumors. Approaches to enhance tumor-infiltrating lymphocytes in the tumor bed may substantially augment clinical immunotherapy responses. In this article, we report that proteolysis of the tolerogenic matrix proteoglycan versican (VCAN) strongly correlated with CD8(+) T cell infiltration in colorectal cancer, regardless of mismatch repair status...
July 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28749573/il-6-stat3-signaling-as-a-promising-target-to-improve-the-efficacy-of-cancer-immunotherapy
#20
REVIEW
Hidemitsu Kitamura, Yosuke Ohno, Yujiro Toyoshima, Junya Ohtake, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi
Overcoming the immunosuppressive state in tumor microenvironments is a critical issue to improve the efficacy of cancer immunotherapy. Interleukin (IL)-6, a pleiotropic cytokine, is highly produced in the tumor-bearing host. Previous studies have indicated that IL-6 suppresses the antigen presentation ability of dendritic cells (DCs) through activation of signal transducer and activator of transcription 3 (STAT3). Thus, we focused on the precise effect of the IL-6/STAT3 signaling cascade on human DCs and the subsequent induction of antitumor T cell immune responses...
July 27, 2017: Cancer Science
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