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https://www.readbyqxmd.com/read/28732046/qualitative-differences-in-cellular-immunogenicity-elicited-by-hepatitis-c-virus-t-cell-vaccines-employing-prime-boost-regimens
#1
Wendy G Tan, Iryna Zubkova, Alla Kachko, Frances Wells, Heiko Adler, Gerd Sutter, Marian E Major
T-cell based vaccines have been considered as attractive candidates for prevention of hepatitis C virus (HCV) infections. In this study we compared the magnitude and phenotypic characteristics of CD8+ T-cells induced by three commonly used viral vectors, Adenovirus-5 (Ad5), Vaccinia virus (VV) and Modified Vaccinia Ankara (MVA) expressing the HCV NS3/4A protein. C57/BL6 mice were primed with DNA expressing NS3/4A and boosted with each of the viral vectors in individual groups of mice. We then tracked the vaccine-induced CD8+ T-cell responses using pentamer binding and cytokine production analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28725220/a-novel-derivative-of-mycousnine-produced-by-the-endophytic-fungus-mycosphaerella-nawae-exhibits-high-and-selective-immunosuppressive-activity-on-t-cells
#2
Li-Wei Wang, Jin-Liang Wang, Jing Chen, Jia-Jie Chen, Jia-Wei Shen, Xiao-Xiao Feng, Christian P Kubicek, Fu-Cheng Lin, Chu-Long Zhang, Feng-Yang Chen
An endophytic fungus, Mycosphaerella nawae ZJLQ129, was isolated from the leaves of the traditional Chinese medicine Smilax china. From the fermentation broth and mycelium, a dibenzofurane compound (-)mycousnine (1) was isolated. Chemical modification of it to the amide derivative (-)mycousnine enamine (2), which is new to science, was found to have high and selective immunosuppressive activity: similar to cyclosporin A, (-)mycousnine enamine (2) selectively inhibited T cell proliferation, suppressed the expression of the surface activation antigens CD25 and CD69 and the formation and expression of the cytokines interleukin-2 as well as interferon γ in activated T cells, but did not show any effect on the proliferation of B cells and cancer cells (PANC-1 and A549) and the activation of macrophages...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28723576/an-atlas-of-human-regulatory-t-helper-like-cells-reveals-features-of-th2-like-tregs-that-support-a-tumorigenic-environment
#3
Leena Halim, Marco Romano, Reuben McGregor, Isabel Correa, Polychronis Pavlidis, Nathali Grageda, Sec-Julie Hoong, Muhammed Yuksel, Wayel Jassem, Rosalind F Hannen, Mark Ong, Olivia Mckinney, Bu'Hussain Hayee, Sophia N Karagiannis, Nicholas Powell, Robert I Lechler, Estefania Nova-Lamperti, Giovanna Lombardi
Regulatory T cells (Tregs) play a pivotal role in maintaining immunological tolerance, but they can also play a detrimental role by preventing antitumor responses. Here, we characterized T helper (Th)-like Treg subsets to further delineate their biological function and tissue distribution, focusing on their possible contribution to disease states. RNA sequencing and functional assays revealed that Th2-like Tregs displayed higher viability and autocrine interleukin-2 (IL-2)-mediated activation than other subsets...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28721449/role-of-regulatory-t-cells-in-acute-myeloid-leukemia-patients-undergoing-relapse-preventive-immunotherapy
#4
Frida Ewald Sander, Malin Nilsson, Anna Rydström, Johan Aurelius, Rebecca E Riise, Charlotta Movitz, Elin Bernson, Roberta Kiffin, Anders Ståhlberg, Mats Brune, Robin Foà, Kristoffer Hellstrand, Fredrik B Thorén, Anna Martner
Regulatory T cells (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3(+)CD25(high)CD4(+) Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival...
July 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28719434/primary-cutaneous-small-medium-cd4-t-cell-lymphoproliferative-disorder-occurring-in-a-patient-with-metastatic-melanoma
#5
Jonathan J Davick, Elizabeth Gaughan, Megan Barry, Alejandro A Gru
Therapeutic agents designed to stimulate the immune system are now cornerstones in the treatment of metastatic melanoma. These drugs promote lymphocyte growth and survival, which could plausibly result in clinical lymphoproliferative disorders. We report the case of a 62-year-old female with metastatic melanoma who developed primary cutaneous small/medium CD4 T-cell lymphoproliferative disorder (PC-SMTCL) after treatment with vemurafenib and recombinant high-dose interleukin-2 (IL-2). The patient developed a painless red papule behind the ear...
July 14, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28719288/evaluation-of-the-protective-effect-of-deoxyribonucleic-acid-vaccines-encoding-granule-antigen-2-and-5-against-acute-toxoplasmosis-in-balb-c-mice
#6
Xiao Teng Ching, Mun Yik Fong, Yee Ling Lau
AbstractToxoplasma gondii infects a broad range of warm-blooded hosts, including humans. Important clinical manifestations include encephalitis in immunocompromised patients as well as miscarriage and fetal damage during early pregnancy. Toxoplasma gondii dense granule antigen 2 and 5 (GRA2 and GRA5) are essential for parasitophorous vacuole development of the parasite. To evaluate the potential of GRA2 and GRA5 as recombinant DNA vaccine candidates, these antigens were cloned into eukaryotic expression vector (pcDNA 3...
June 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28719267/comparison-of-cytokine-responses-in-ecuadorian-children-infected-with-giardia-ascaris-or-both-parasites
#7
Jill Weatherhead, Andrea Arévalo Cortés, Carlos Sandoval, Maritza Vaca, Martha Chico, Sophia Loor, Philip J Cooper, Rojelio Mejia
AbstractMore than 2 billion people are infected with parasites globally, and the majority have coinfections. Intestinal protozoa and helminths induce polarizing CD4(+) T-helper cell 1 (Th1) mediated cytokine responses within the host. Such immune polarization may inhibit the ability of the host to mount an adequate immune response for pathogen clearance to concurrent pathogens. The current study evaluated the plasma cytokine profile in Ascaris and Giardia coinfected children compared with Giardia- and Ascaris-only infected children...
June 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28717087/pulmonary-intravascular-large-b-cell-lymphoma-ivlbcl-disguised-as-an-asthma-exacerbation-in-a-patient-with-asthma
#8
Tomohito Takeshige, Norihiro Harada, Yasuhito Sekimoto, Ryota Kanemaru, Takeo Tsutsumi, Kei Matsuno, Satomi Shiota, Azuchi Masuda, Akihiko Gotoh, Miki Asahina, Toshimasa Uekusa, Kazuhisa Takahashi
A 62-year-old man with asthma presented with a 1-month history of wheezing and exertional dyspnea. Although the wheezing symptoms disappeared after systemic corticosteroid therapy, the exertional dyspnea and hypoxemia did not improve. A diagnosis of intravascular large B-cell lymphoma (IVLBCL) with pulmonary involvement was suspected because of the increased serum lactic dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R) level, increased alveolar-arterial oxygen difference (AaDO2), decreased pulmonary diffusing capacity for carbon monoxide (DLCO) and scintigraphic, computed tomography (CT) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT findings...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28716814/potency-matched-dual-cytokine-antibody-fusion-proteins-for-cancer-therapy
#9
Roberto De Luca, Alex Soltermann, Francesca Pretto, Catherine Pemberton-Ross, Giovanni Pellegrini, Sarah Wulhfard, Dario Neri
A novel biopharmaceutical, consisting of the F8 monoclonal antibody (specific to a splice isoform of fibronectin) simultaneously fused to both tumor necrosis factor and interleukin-2, was found to react with the majority of solid tumors and hematological malignancies in mouse and man, but not with healthy adult tissues. The product selectively localized to neoplastic lesions in vivo, as evidenced by quantitative biodistribution studies using radioiodinated protein preparations. When the potency of the cytokine payloads was matched by a single-point mutation, the resulting fusion protein (IL2-F8-TNF(mut)) eradicated soft-tissue sarcomas in immunocompetent mice, which did not respond to individual antibody-cytokine fusion proteins or by standard doxorubicin treatment...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28715277/superantigen-staphylococcal-enterotoxin-c1-inhibits-the-growth-of-bladder-cancer
#10
Tao Liu, Lin Li, Lei Yin, Hongyuan Yu, Hongwei Jing, Yang Liu, Chuize Kong, Mingkai Xu
Superantigens can induce cell-mediated cytotoxicity preferentially against MHC II-positive target cells with large amounts of inflammatory cytokines releasing. In this study, superantigen staphylococcal enterotoxin C (SEC) 1 was investigated to evaluate its potential in bladder cancer immunotherapy in vitro and in vivo. Our results revealed that SEC1 could stimulate the proliferation of human peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner, accompanied with the release of interleukin-2, interferon-γ, and tumor necrosis factor-α, and increased the population of CD4(+) T cells and CD8(+) T cells...
July 17, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28713391/apoptosis-induced-via-gamma-delta-t-cell-antigen-receptor-blocking-antibodies-a-cautionary-tale
#11
Indrani Dutta, Lynne-Marie Postovit, Gabrielle M Siegers
Mechanistic studies contribute greatly to our understanding of γδ T cell (γδTc) biology, aiding development of these cells as immunotherapeutic agents. The antibody blocking assay is an accepted method to determine the receptors involved in γδTc killing of tumor targets. Effectors and/or targets are preincubated with microgram quantities of monoclonal antibodies (mAb), often described by commercial sources to be useful for blocking assays. We and others have used such assays extensively in the past, correlating decreases in cytotoxicity against specific targets with involvement of the blocked receptor(s)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28713023/an-extended-mathematical-model-of-tumor-growth-and-its-interaction-with-the-immune-system-to-be-used-for-developing-an-optimized-immunotherapy-treatment-protocol
#12
Milad Qomlaqi, Fariba Bahrami, Maryam Ajami, Jamshid Hajati
BACKGROUND: Chemotherapy is usually known as the main modality for cancer treatment. Nevertheless, most of chronic cancers could not be treated with chemotherapy alone. Immunotherapy is a new modality for cancer treatment that is effective for early stages of cancer and it has fewer side effects compared to chemotherapy, specifically for those types of cancer that are resistant to it. METHOD: This work presents an extended mathematical model to depict interactions between cancerous and adaptive immune system in mouse...
July 14, 2017: Mathematical Biosciences
https://www.readbyqxmd.com/read/28711483/a-multistage-subunit-vaccine-effectively-protects-mice-against-primary-progressive-tuberculosis-latency-and-reactivation
#13
Jilei Ma, Xindong Teng, Xiaochun Wang, Xionglin Fan, Yaqi Wu, Maopeng Tian, Zijie Zhou, Longmeng Li
Adult tuberculosis (TB) is the main cause of TB epidemic and death. The infection results mainly by endogenous reactivation of latent TB infection and secondarily transmitted by exogenous infection. There is no vaccine for adult TB. To this end, we first chose antigens from a potential antigenic reservoir. The antigens strongly recognized T cells from latent and active TB infections that responded to antigens expressed by Mycobacterium tuberculosis cultured under different metabolic states. Fusions of single-stage polyprotein CTT3H, two-stage polyprotein A1D4, and multistage CMFO were constructed...
July 8, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28693575/interleukin-2-enhancer-binding-factor-2-interacts-with-the-nsp9-or-nsp2-of-porcine-reproductive-and-respiratory-syndrome-virus-and-exerts-negatively-regulatory-effect-on-the-viral-replication
#14
Xuexia Wen, Ting Bian, Zhibang Zhang, Lei Zhou, Xinna Ge, Jun Han, Xin Guo, Hanchun Yang, Kangzhen Yu
BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive failures in sows and respiratory diseases in growing pigs, resulting in huge economic loss for the pig production worldwide. The nonstructural protein 9 (nsp9) and nonstructural protein 2 (nsp2) of PRRSV are known to play important roles in viral replication. Cellular interleukin-2 enhancer binding factor 2 (ILF2) participates in many cellular pathways and involves in life cycle of some viruses...
July 11, 2017: Virology Journal
https://www.readbyqxmd.com/read/28684674/dietary-chlorella-vulgaris-ameliorates-altered-immunomodulatory-functions-in-cyclophosphamide-induced-immunosuppressive-mice
#15
Dai Cheng, Zhaodong Wan, Xinyu Zhang, Jian Li, He Li, Chunling Wang
Based on the well-known toxicity of cyclophosphamide (CYP) on the immune system, this research investigated the modulating effects of the long-term dietary Chlorella vulgaris (CV) supplementation on the immunosuppression induced by CYP in mice, in order to provide a novel dietary design to mitigate the side effects of CYP therapy. Control, CYP-treated, CYP + CV (6%), CYP + CV (12%) and CYP + CV (24%) were used for 6 weeks, CV supplement in diet recovered the significantly reduced immunological function in CYP treated mice...
July 6, 2017: Nutrients
https://www.readbyqxmd.com/read/28681703/hybrid-approach-to-model-the-spatial-regulation-of-t-cell-responses
#16
Anass Bouchnita, Gennady Bocharov, Andreas Meyerhans, Vitaly Volpert
BACKGROUND: Moving from the molecular and cellular level to a multi-scale systems understanding of immune responses requires the development of novel approaches to integrate knowledge and data from different biological levels into mechanism-based integrative mathematical models. The aim of our study is to present a methodology for a hybrid modelling of immunological processes in their spatial context. METHODS: A two-level hybrid mathematical model of immune cell migration and interaction integrating cellular and organ levels of regulation for a 2D spatial consideration of idealized secondary lymphoid organs is developed...
June 21, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28681030/novel-immunotherapy-in-metastatic-renal-cell-carcinoma
#17
REVIEW
Yang Hyun Cho, Myung Soo Kim, Ho Seok Chung, Eu Chang Hwang
Despite the rapid development of therapeutic modalities for metastatic renal cell carcinoma (mRCC) over the past decade to include a number of targeted antiangiogenic therapies and traditional immunotherapy, such as high-dose interleukin-2 and interferon-α, mRCC continues to be associated with poor prognosis. Currently, several novel immunotherapy agents, such as cancer vaccines, adoptive cell therapy, and checkpoint inhibitors, such as programmed cell death-1 (PD-1 present on T cells), one of its ligands (PD-L1 present on antigen-presenting cells and tumor cells), and cytotoxic T-lymphocyte-associated protein-4 pathways, are being studied in mRCC and are showing promise as important steps in the management of this disease...
July 2017: Investigative and Clinical Urology
https://www.readbyqxmd.com/read/28679969/incidence-of-spontaneous-lymphomas-in-non-experimental-nod-shi-scid-il-2r%C3%AE-null-nog-mice
#18
Masahiko Yasuda, Tomoyuki Ogura, Takayuki Goto, Mika Yagoto, Yoko Kamai, Chie Shimomura, Nobuhito Hayashimoto, Yukito Kiyokawa, Hideki Shinohara, Riichi Takahashi, Kenji Kawai
Severely immunodeficient NOD/Shi-scid, IL-2Rγ(null) (NOG) mice provide an in vivo model for human cell/tissue transplantation studies. NOG mice were established by combining interleukin-2 receptor-γ chain knockout mice and NOD/Shi-scid mice. They exhibit a high incidence of thymic lymphomas and immunoglobulin (Ig) leakiness. In this study, we assessed the incidence of malignant lymphomas and the occurrence of leakiness in 2,184 non-experimental NOG retired breeder mice aged 16-40 weeks. We established that the total incidence of lymphomas was only 0...
July 6, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28678791/modeling-the-receptor-pharmacology-pharmacokinetics-and-pharmacodynamics-of-nktr-214-a-kinetically-controlled-interleukin-2-il2-receptor-agonist-for-cancer-immunotherapy
#19
Deborah Charych, Samira Khalili, Vidula Dixit, Peter Kirk, Thomas Chang, John Langowski, Werner Rubas, Stephen K Doberstein, Michael Eldon, Ute Hoch, Jonathan Zalevsky
Cytokines are potent immune modulating agents but are not ideal medicines in their natural form due to their short half-life and pleiotropic systemic effects. NKTR-214 is a clinical-stage biologic that comprises interleukin-2 (IL2) protein bound by multiple releasable polyethylene glycol (PEG) chains. In this highly PEG-bound form, the IL2 is inactive; therefore, NKTR-214 is a biologic prodrug. When administered in vivo, the PEG chains slowly release, creating a cascade of increasingly active IL2 protein conjugates bound by fewer PEG chains...
2017: PloS One
https://www.readbyqxmd.com/read/28678311/regulation-of-mir-92a-on-vascular-endothelial-aging-via-mediating-nrf2-keap1-are-signal-pathway
#20
H Liu, H-Y Wu, W-Y Wang, Z-L Zhao, X-Y Liu, L-Y Wang
OBJECTIVE: Various human aging-related diseases start with vascular aging, in which the aging of vascular endothelium is the first step to cause a structural and functional deficit of vascular endothelium, leading to vascular disorders. MicroRNA (miR) participates in various processes of body development and pathological processes via mediating cell proliferation, differentiation, and apoptosis. A previous study showed the correlation between cardiovascular disease and miR-92a, whose role and mechanism in vascular endothelial aging has not been reported...
June 2017: European Review for Medical and Pharmacological Sciences
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