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https://www.readbyqxmd.com/read/30017877/adenovirus-coding-for-interleukin-2-and-tumor-necrosis-factor-alpha-replaces-lymphodepleting-chemotherapy-in-adoptive-t-cell-therapy
#1
João Manuel Santos, Víctor Cervera-Carrascon, Riikka Havunen, Sadia Zafar, Mikko Siurala, Suvi Sorsa, Marjukka Anttila, Anna Kanerva, Akseli Hemminki
Lymphodepleting preconditioning with high-dose chemotherapy is commonly used to increase the clinical efficacy of adoptive T cell therapy (ACT) strategies, however, with severe toxicity for patients. Conversely, oncolytic adenoviruses are safe and, when engineered to express interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-α), they can achieve antitumor immunomodulatory effects similar to lymphodepletion. Therefore, we compare the safety and efficacy of such adenoviruses with a cyclophosphamide- and fludarabine-containing lymphodepleting regimen in the setting of ACT...
July 12, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/30016182/differential-expression-of-immune-inhibitory-checkpoint-signatures-on-antiviral-and-inflammatory-t-cell-populations-in-chronic-hepatitis-b
#2
Helen Cooksley, Antonio Riva, Krum Katzarov, Tanya Hadzhiolova-Lebeau, Slava Pavlova, Marieta Simonova, Roger Williams, Shilpa Chokshi
Virus-specific T cells are critical in mediating the pathogenesis of hepatitis B virus (HBV) infection. Interferon gamma (IFNγ)-producing T cells are associated with resolution; in contrast, interleukin-17 (IL-17)-producing T cells are linked to exacerbation of liver inflammation and injury. Checkpoint receptors stringently regulate T cell functions, with their expression profiles varying on different T cell subsets. Blockade of checkpoint receptors may be an effective therapeutic strategy for chronic hepatitis B (CHB); however, blockade may also inadvertently exacerbate proinflammatory responses...
July 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/30015237/comparison-of-six-cell-penetrating-peptides-with-different-properties-for-in-vitro-and-in-vivo-delivery-of-hpv16-e7-antigen-in-therapeutic-vaccines
#3
Sepideh Shahbazi, Azam Bolhassani
The high risk human papillomavirus (HPV) types 16 and 18 are globally linked to >50% and 20% of all cervical cancers, respectively. The HPV E7 oncoprotein was determined as a therapeutic vaccine target due to its constitutive expression by HPV-infected cells. The findings demonstrated the efficiency of therapeutic HPV DNA- and protein-based vaccines in preclinical and clinical trials. However, there are limitations for penetration of DNA and protein constructs into the cells without a suitable delivery system...
July 13, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/30015235/switched-memory-b-cells-promote-alveolar-bone-damage-during-periodontitis-an-adoptive-transfer-experiment
#4
Yakun Han, Ying Jin, Yibin Miao, Tie Shi, Xiaoping Lin
Periodontitis is a bacteria-induced disease that often leads to alveolar bone damage. We sought to determine the role and mechanism of switched memory B cells in alveolar bone destruction during periodontitis. Sensitized B cells were sorted and cultured, then their expression of receptor activator for nuclear factor-κB ligand (RANKL), interleukin-6 (IL-6), and interleukin-12 (IL-12) was detected. Using these cells, we prepared adoptive transfer models in which we induced periodontitis. We found that switched memory B cells produced more RANKL in terms of both protein and mRNA levels than other subpopulations...
July 12, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/30014604/vitamin-k1-and-vitamin-k2-immunopharmacological-effects-on-the-peripheral-lymphocytes-of-healthy-subjects-and-dialysis-patients-as-estimated-by-the-lymphocyte-immunosuppressant-sensitivity-test
#5
Junichi Kusano, Sachiko Tanaka, Hiroto Matsuda, Yoshikazu Hara, Yoshiaki Fujii, Shinya Suzuki, Masao Sekiyama, Eiki Ando, Kentaro Sugiyama, Toshihiko Hirano
WHAT IS KNOWN AND OBJECTIVE: Renal transplant recipients receive immunosuppressive therapy to prevent acute rejection. We evaluated the immunopharmacological efficacy of vitamin K1 (VK1) and vitamin K2 (VK2) on T-cell mitogen-activated-peripheral lymphocytes of dialysis patients and healthy subjects. METHODS: The effects of VK1 and VK2 on the T-cell mitogen-stimulated proliferation of peripheral blood mononuclear cells (PBMCs) obtained from 12 healthy subjects and 12 dialysis patients were estimated...
July 16, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/30014237/preclinical-evaluation-of-an-innovative-anti-tam-approach-based-on-zoledronate-loaded-erythrocytes
#6
Raffaella Sabatino, Serafina Battistelli, Mauro Magnani, Luigia Rossi
In tumor microenvironment, tumor-associated macrophages (TAMs) are implicated in cancer sustainment, metastasis, and drug resistance, raising a growing interest as targets in cancer therapy. Since the bisphosphonate zoledronate has proven to affect TAMs' functions, the anti-tumor effect of single or repeated administrations of red blood cells (RBCs) encapsulating zoledronate was evaluated in a mouse model of mammary carcinoma. The obtained results showed that loaded RBCs, but not free zoledronate, caused a significant (p < 0...
July 16, 2018: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/30013952/transcriptional-profiling-of-immune-related-genes-in-leishmania-infantum-infected-mice-identification-of-potential-biomarkers-of-infection-and-progression-of-disease
#7
Eduardo Ontoria, Yasmina E Hernández-Santana, Ana C González-García, Manuel C López, Basilio Valladares, Emma Carmelo
Leishmania spp. is a protozoan parasite that affects millions of people around the world. At present, there is no effective vaccine to prevent leishmaniases in humans. A major limitation in vaccine development is the lack of precise understanding of the particular immunological mechanisms that allow parasite survival in the host. The parasite-host cell interaction induces dramatic changes in transcriptome patterns in both organisms, therefore, a detailed analysis of gene expression in infected tissues will contribute to the evaluation of drug and vaccine candidates, the identification of potential biomarkers, and the understanding of the immunological pathways that lead to protection or progression of disease...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/30013570/evaluating-the-vaccine-potential-of-a-tetravalent-fusion-protein-rbm-haxt-vaccine-antigen-against-lymphatic-filariasis-in-a-mouse-model
#8
Nikhil Chauhan, Vishal Khatri, Priyankana Banerjee, Ramaswamy Kalyanasundaram
Lymphatic filariasis (LF) is a tropical parasitic infection of human transmitted by mosquitoes. Chronic infection results in severe physical disability in the infected patients. Although several potential vaccine antigens were identified by several groups, there are no licensed prophylactic vaccine to date against this infection in the human. Previous attempts from our laboratory to develop a trivalent prophylactic vaccine against LF showed that >90% protection could be achieved in rodent models. However, this trivalent vaccine gave only 35% protection in non-human primates...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30013275/oral-intake-of-lactobacillus-helveticus-ns8-alleviates-ovalbumin-induced-atopic-dermatitis-in-skh-1-hairless-mice
#9
Jingjing Rong, Shuzhan Liu, Chao Hu, Feng Jin, Li Wang
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and is driven by strong type 2 immune responses. Lactobacillus helveticus NS8 (NS8), a probiotic strain isolated from Mongolian koumiss, has anti-inflammatory activities. Here, we evaluated the therapeutic potential of NS8 on AD-like skin lesions by using SKH-1 hairless mice that underwent three cycles of epicutaneous sensitization (EC) with ovalbumin (OVA). NS8 (5 × 108 CFU/day) was orally administered to mice from 2 weeks before the first sensitization until the end of the study...
September 2018: Indian Journal of Microbiology
https://www.readbyqxmd.com/read/30013034/activation-of-natural-killer-t-cells-contributes-to-triptolide-induced-liver-injury-in-mice
#10
Xin-Zhi Wang, Ru-Feng Xue, Shen-Ye Zhang, Ya-Ting Zheng, Lu-Yong Zhang, Zhen-Zhou Jiang
Triptolide (TP) is the main active ingredient of Tripterygium wilfordii Hook.f, which has attracted great interest due to its promising efficacy for autoimmune diseases and tumors. However, severe adverse reactions, especially hepatotoxicity, have restricted its approval in the market. In the present study we explored the role of hepatic natural killer T (NKT) cells in the pathogenesis of TP-induced liver injury in mice. TP (600 μg/kg/day, i.g.) was administered to female mice for 1, 3, or 5 days. We found that administration of TP dose-dependently induced hepatotoxicity, evidenced by the body weight reduction, elevated serum ALT and AST levels, as well as significant histopathological changes in the livers...
July 16, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/30012585/tnp-470-skews-dc-differentiation-to-th1-stimulatory-phenotypes-and-can-serve-as-a-novel-adjuvant-in-a-cancer-vaccine
#11
Derek Hoi-Hang Ho, Roger Hoi-Fung Wong
Fumagillin is an antiangiogenic and antineoplastic fungal natural product, and TNP-470 is one of its most potent analogs. Decades of studies revealed that TNP-470 has potent anticancer activities via destruction of neovasculature. In stark contrast, TNP-470 has been reported to suppress lymphocyte proliferation, thereby limiting its clinical potentials. In an attempt to investigate whether the similar or opposite immunomodulatory effect of TNP-470 could act on myeloid cells, we found that TNP-470 potentiates the immunogenicity of dendritic cells (DCs) toward a phenotype with T helper cell type 1 (Th1)-stimulatory features...
July 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/30012242/mast-cells-stimulated-with-peptidoglycan-from-staphylococcus-aureus-augment-the-development-of-th1-cells
#12
Katsuhiko Matsui, Saeko Kanai, Manami Ikuta, Saki Horikawa
BACKGROUND: The skin of patients with atopic dermatitis (AD) is superficially colonized by Staphylococcus aureus. We have previously found that percutaneous permeation of peptidoglycan (PEG) from S. aureus increases the number of mast cells in the dermis, as seen in skin lesions of AD patients. The purpose of the present study was to clarify the influence of PEG on T helper type 1 (Th1)/ T helper type 2 (Th2) cell development mediated by mast cells. METHODS: Mast cells were induced by long-term culture of murine spleen cells in medium supplemented with tumor necrosis factor (TNF)- a...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/30012158/an-ifn%C3%AE-cxcl2-regulatory-pathway-determines-lesion-localization-during-eae
#13
Joshua S Stoolman, Patrick C Duncker, Amanda K Huber, David A Giles, Jesse M Washnock-Schmid, Athena M Soulika, Benjamin M Segal
BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG)-reactive T-helper (Th)1 cells induce conventional experimental autoimmune encephalomyelitis (cEAE), characterized by ascending paralysis and monocyte-predominant spinal cord infiltrates, in C57BL/6 wildtype (WT) hosts. The same T cells induce an atypical form of EAE (aEAE), characterized by ataxia and neutrophil-predominant brainstem infiltrates, in syngeneic IFNγ receptor (IFNγR)-deficient hosts. Production of ELR+ CXC chemokines within the CNS is required for the development of aEAE, but not cEAE...
July 16, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/30011861/vitamin-d-regulates-maternal-t-helper-cytokine-production-in-infertile-women
#14
Yuko Ikemoto, Keiji Kuroda, Koji Nakagawa, Asako Ochiai, Rie Ozaki, Keisuke Murakami, Makoto Jinushi, Akemi Matsumoto, Rikikazu Sugiyama, Satoru Takeda
Vitamin D (VD) deficiency is associated with reproductive failure. However, the relationship between VD and maternal immunity remains unclear. We investigated the clinical efficacy of VD in maternal T-helper (Th) cytokines in 276 infertile women and examined for Th1 and Th2 cells based on the deficient, insufficient, and sufficient serum 25-hydroxyvitamin D3 (25[OH]VD) levels (<12, 12⁻30, and >30 ng/mL, respectively). Most infertile women had a low-level of VD (87.3%). Immunological tests of pre-/post-VD supplementation were performed in patients who were deficient and insufficient in VD...
July 13, 2018: Nutrients
https://www.readbyqxmd.com/read/30011369/co-delivery-of-doxorubicin-and-interferon-gamma-by-thermosensitive-nanoparticles-for-cancer-immunochemotherapy
#15
Yijia Yin, Qian Hu, Chenfeng Xu, Qi Qiao, Xianya Qin, Qingle Song, Yang Peng, Yongdan Zhao, Zhiping Zhang
A dual-sensitive nanoparticle delivery system was constructed by incorporating acid sensitive hydrazone linker into thermosensitive nanoparticles (TSNs) for co-encapsulating doxorubicin (DOX) and interferon γ (IFNγ), to realize co-delivery of chemotherapy and immunotherapy agents against melanoma. DOX, a chemotherapeutic drug, was conjugated to TSNs by a pH-sensitive chemical bond and IFNγ, a potent immune-modulator, was absorbed into TSNs through the thermosensitivity and electrostatics of nanoparticles...
July 16, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/30010888/goblet-cell-produced-retinoic-acid-suppresses-cd86-expression-and-il-12-production-in-bone-marrow-derived-cells
#16
Yangyan Xiao, Cintia S De Paiva, Zhiyuan Yu, Rodrigo Guimaraes de Souza, De-Quan Li, Stephen C Pflugfelder
Conjunctival goblet cell loss in ocular surface diseases is accompanied by increased number of IL-12 producing antigen presenting cells (APC) and increased IFN- expression. This study tested the hypothesis that mouse conjunctival goblet cells produce biologically active retinoic acid (RA) that suppresses CD86 expression and IL-12 production by myeloid cells. We found conditioned media from cultured conjunctival goblet cells (CjCM) suppressed stimulated CD86 expression, NF-κB p65 activation and IL-12 and IFN- production in unstimulated and LPS-stimulated cultured bone marrow derived cells containing a mixed population of APCs...
July 12, 2018: International Immunology
https://www.readbyqxmd.com/read/30010623/p2x7r-mutation-disrupts-the-nlrp3-mediated-th-program-and-predicts-poor-cardiac-allograft-outcomes
#17
Francesca D'Addio, Andrea Vergani, Luciano Potena, Anna Maestroni, Vera Usuelli, Moufida Ben Nasr, Roberto Bassi, Sara Tezza, Sergio Dellepiane, Basset El Essawy, Maria Iascone, Attilio Iacovoni, Laura Borgese, Kaifeng Liu, Gary Visner, Sirano Dhe-Paganon, Domenico Corradi, Reza Abdi, Randall C Starling, Franco Folli, Gian Vincenzo Zuccotti, Mohamed H Sayegh, Peter S Heeger, Anil Chandraker, Francesco Grigioni, Paolo Fiorina
Purinergic receptor-7 (P2X7R) signaling controls Th17 and Th1 generation/differentiation, while NOD-like receptor P3 (NLRP3) acts as a Th2 transcriptional factor. Here, we demonstrated the existence of a P2X7R/NLRP3 pathway in T cells that is dysregulated by a P2X7R intracellular region loss-of-function mutation, leading to NLRP3 displacement and to excessive Th17 generation due to abrogation of the NLRP3-mediated Th2 program. This ultimately resulted in poor outcomes in cardiac-transplanted patients carrying the mutant allele, who showed abnormal Th17 generation...
July 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/30006528/neutralization-of-the-plasmodium-encoded-mif-ortholog-confers-protective-immunity-against-malaria-infection
#18
Alvaro Baeza Garcia, Edwin Siu, Tiffany Sun, Valerie Exler, Luis Brito, Armin Hekele, Gib Otten, Kevin Augustijn, Chris J Janse, Jeffrey B Ulmer, Jürgen Bernhagen, Erol Fikrig, Andrew Geall, Richard Bucala
Plasmodium species produce an ortholog of the cytokine macrophage migration inhibitory factor, PMIF, which modulates the host inflammatory response to malaria. Using a novel RNA replicon-based vaccine, we show the impact of PMIF immunoneutralization on the host response and observed improved control of liver and blood-stage Plasmodium infection, and complete protection from re-infection. Vaccination against PMIF delayed blood-stage patency after sporozoite infection, reduced the expression of the Th1-associated inflammatory markers TNF-α, IL-12, and IFN-γ during blood-stage infection, augmented Tfh cell and germinal center responses, increased anti-Plasmodium antibody titers, and enhanced the differentiation of antigen-experienced memory CD4 T cells and liver-resident CD8 T cells...
July 13, 2018: Nature Communications
https://www.readbyqxmd.com/read/30004859/connection-between-%C3%AE-%C3%AE-t-cell-and-adenosine-mediated-immune-regulation-in-the-pathogenesis-of-experimental-autoimmune-uveitis
#19
Dongchun Liang, Hui Shao, Willi K Born, Rebecca L O'Brien, Henry J Kaplan, Deming Sun
Regulatory effects of γδ T-cells on immune responses have been studied for years. We have investigated the regulatory effect of γδ T-cells on Th1 and Th17 autoimmune responses, and have studied molecular and cellular mechanisms by which γδ T-cells enhance or inhibit immune responses, exploiting a well-characterized murine model of experimental autoimmune uveitis (EAU). Our results show that (1) aberrant γδ T-cell activation is an important pathogenic event in EAU; (2) γδ T-cells have a unique regulatory effect on Th17 autoimmune responses, which is shaped by the activation status of γδ T-cells; and (3) γδ-mediated immunoregulation is closely linked with the extracellular adenosine metabolism...
2018: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/30003413/subpopulation-structure-of-ifn%C3%AE-producing-t-lymphocytes-in-patients-with-pulmonary-tuberculosis
#20
T E Kononova, O I Urazova, V V Novitskii, I E Esimova, E G Churina
The study of subpopulation structure of IFNγ-producing T cells in patients with pulmonary tuberculosis revealed a decrease in the number of CD3+ IFNγ+ cells against the background of significantly increased IFNγ secretion in vitro irrespective of the clinical form of the disease and drug sensitivity of M. tuberculosis, most strongly expressed in case of the disseminated tuberculosis. In patients with infiltrative drug-sensitive and drug-resistant pulmonary tuberculosis, increased number of Th1/Th17 lymphocytes (CD4+ IFNγ+ IL-17A+ ) and, conversely, decreased number of blood γδT cells was detected...
July 12, 2018: Bulletin of Experimental Biology and Medicine
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