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https://www.readbyqxmd.com/read/28533941/changes-in-clinical-laboratory-parameters-and-pharmacodynamic-markers-in-response-to-blinatumomab-treatment-of-patients-with-relapsed-refractory-all
#1
Virginie Nägele, Andrea Kratzer, Gerhard Zugmaier, Chris Holland, Youssef Hijazi, Max S Topp, Nicola Gökbuget, Patrick A Baeuerle, Peter Kufer, Andreas Wolf, Matthias Klinger
BACKGROUND: Blinatumomab has shown a remission rate of 69% in an exploratory single-arm, phase II dose-escalation study in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We evaluated changes in laboratory parameters and immunopharmacodynamic markers in patients who received blinatumomab in the exploratory phase II study. METHODS: Data from 36 adults with relapsed/refractory ALL receiving blinatumomab as 4-week continuous IV infusions in various dose cohorts were analyzed for changes in liver enzymes, first-dose parameters, peripheral blood cell subpopulations, and cytokine/granzyme B release...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28533445/lung-cd4-tissue-resident-memory-t-cells-mediate-adaptive-immunity-induced-by-previous-infection-of-mice-with-bordetella-pertussis
#2
Mieszko M Wilk, Alicja Misiak, Róisín M McManus, Aideen C Allen, Marina A Lynch, Kingston H G Mills
Th1 and Th17 cells have an established role in protective immunity to Bordetella pertussis, but this evidence is based largely on peripheral T cells. There is emerging evidence that local tissue-resident memory T (TRM) cells that accumulate in tissue following mucosal infection may be crucial for long-term immunity. In this study, we examined the role of respiratory CD4 TRM cells in immunity to B. pertussis Natural immunity to B. pertussis induced by infection is considered long lasting and effective at preventing reinfection...
May 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28533414/manipulating-dna-damage-response-signaling-for-the-treatment-of-immune-mediated-diseases
#3
Jonathan P McNally, Scott H Millen, Vandana Chaturvedi, Nora Lakes, Catherine E Terrell, Eileen E Elfers, Kaitlin R Carroll, Simon P Hogan, Paul R Andreassen, Julie Kanter, Carl E Allen, Michael M Henry, Jay N Greenberg, Stephan Ladisch, Michelle L Hermiston, Michael Joyce, David A Hildeman, Jonathan D Katz, Michael B Jordan
Antigen-activated lymphocytes undergo extraordinarily rapid cell division in the course of immune responses. We hypothesized that this unique aspect of lymphocyte biology leads to unusual genomic stress in recently antigen-activated lymphocytes and that targeted manipulation of DNA damage-response (DDR) signaling pathways would allow for selective therapeutic targeting of pathological T cells in disease contexts. Consistent with these hypotheses, we found that activated mouse and human T cells display a pronounced DDR in vitro and in vivo...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533093/safety-and-immunogenicity-of-a-live-attenuated-influenza-h5-candidate-vaccine-strain-a-17-turkey-turkey-05-133-h5n2-and-its-priming-effects-for-potential-pre-pandemic-use-a-randomised-double-blind-placebo-controlled-trial
#4
Punnee Pitisuttithum, Kobporn Boonnak, Supat Chamnanchanunt, Pilaipan Puthavathana, Viravarn Luvira, Hatairat Lerdsamran, Jaranit Kaewkungwal, Saranath Lawpoolsri, Vipa Thanachartwet, Udomsak Silachamroon, Wanibtisam Masamae, Alexandra Schuetz, Ponthip Wirachwong, Sit Thirapakpoomanunt, Larisa Rudenko, Erin Sparrow, Martin Friede, Marie-Paule Kieny
BACKGROUND: The emergence of highly pathogenic avian influenza H5N1 viruses has raised concerns about their pandemic potential. Vaccination is the most effective way of preventing influenza. In this study, we investigated the safety and immunogenicity of an avian H5N2 live attenuated influenza vaccine (LAIV H5N2) in healthy Thai adults and its priming immune responses with an H5N1 inactivated vaccine boost. METHODS: This study was done at the Vaccine Trial Centre at Mahidol University, Bangkok, Thailand and was divided into two parts...
May 19, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28530241/notch-mediated-conversion-of-activated-t-cells-into-stem-cell-memory-like-t-cells-for-adoptive-immunotherapy
#5
Taisuke Kondo, Rimpei Morita, Yuumi Okuzono, Hiroko Nakatsukasa, Takashi Sekiya, Shunsuke Chikuma, Takashi Shichita, Mitsuhiro Kanamori, Masato Kubo, Keiko Koga, Takahiro Miyazaki, Yoshiaki Kassai, Akihiko Yoshimura
Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8(+) TSCM cells can be generated in vitro from naive CD8(+) T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM-like cells in vitro (iTSCM cells) from activated CD4(+) and CD8(+) T cells in mice and humans by coculturing with stromal cells that express a Notch ligand...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529952/advancements-in-developing-strategies-for-sterilizing-and-functional-hiv-cures
#6
REVIEW
Wei Xu, Haoyang Li, Qian Wang, Chen Hua, Hanzhen Zhang, Weihua Li, Shibo Jiang, Lu Lu
Combined antiretroviral therapy (cART) has been successful in prolonging lifespan and reducing mortality of patients infected with human immunodeficiency virus (HIV). However, the eradication of latent HIV reservoirs remains a challenge for curing HIV infection (HIV cure) because of HIV latency in primary memory CD4(+) T cells. Currently, two types of HIV cures are in development: a "sterilizing cure" and a "functional cure." A sterilizing cure refers to the complete elimination of replication-competent proviruses in the body, while a functional cure refers to the long-term control of HIV replication without treatment...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28529928/the-probiotic-compound-vsl-3-modulates-mucosal-peripheral-and-systemic-immunity-following-murine-broad-spectrum-antibiotic-treatment
#7
Ira Ekmekciu, Eliane von Klitzing, Ulrike Fiebiger, Christian Neumann, Petra Bacher, Alexander Scheffold, Stefan Bereswill, Markus M Heimesaat
There is compelling evidence linking the commensal intestinal microbiota with host health and, in turn, antibiotic induced perturbations of microbiota composition with distinct pathologies. Despite the attractiveness of probiotic therapy as a tool to beneficially alter the intestinal microbiota, its immunological effects are still incompletely understood. The aim of the present study was to assess the efficacy of the probiotic formulation VSL#3 consisting of eight distinct bacterial species (including Streptococcus thermophilus, Bifidobacterium breve, B...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28529001/a-single-intranasal-administration-of-virus-like-particle-vaccine-induces-an-efficient-protection-for-mice-against-human-respiratory-syncytial-virus
#8
Yue-Ying Jiao, Yuan-Hui Fu, Yi-Fei Yan, Ying Hua, Yao Ma, Xiu-Juan Zhang, Jing-Dong Song, Xiang-Lei Peng, Jiaqiang Huang, Tao Hong, Jin-Sheng He
Human respiratory syncytial virus (RSV) is an important pediatric pathogen causing acute viral respiratory disease in infants and young children. However, no licensed vaccines are currently available. Virus-like particles (VLPs) may bring new hope to producing RSV VLP vaccine with high immunogenicity and safety. Here, we constructed the recombinants of matrix protein (M) and fusion glycoprotein (F) of RSV, respectively into a replication-deficient first-generation adenoviral vector (FGAd), which were used to co-infect Vero cells to assemble RSV VLPs successfully...
May 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28528253/pressure-induced-transformations-in-sorbic-acid
#9
G D Saraiva, J R Maia, J A Lima, C E S Nogueira, P T C Freire, F F de Sousa, A M R Teixeira, J Mendes Filho
This research reports a pressure dependent Raman study of the sorbic acid between 0.0 and 10.0GPa. The unpolarized Raman spectra were measured in the spectral range of 20-3000cm(-1). The high-pressure Raman scattering study of the sorbic acid showed that it underwent a gradual, disordering process. At the room temperature and at the ambient pressure conditions, the crystal structure of the sorbic acid belongs to the monoclinic system with a C2/c (C2h(6)) space group. The pressure increase induced a higher disorder in the monoclinic unit cell, since a single bending mode, and only very broad stretching Raman modes are present at pressure of ~10GPa...
May 10, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28527688/clinical-development-of-a-var2csa-based-placental-malaria-vaccine-pamvac-quantifying-vaccine-antigen-specific-memory-b-t-cell-activity-in-beninese-primigravidae
#10
Komi Gbédandé, Nadine Fievet, Firmine Viwami, Sem Ezinmegnon, Saadou Issifou, Jean-Philippe Chippaux, Yannelle Dossou, Kabirou Moutairou, Achille Massougbodji, Nicaise Ndam, Willem Adriaan de Jongh, T Max M Søgaard, Ali Salanti, Morten A Nielsen, Meral Esen, Benjamin Mordmüller, Philippe Deloron, Adrian J F Luty
BACKGROUND: The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum. A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC's clinical development, we quantified naturally acquired vaccine antigen-specific memory B and T cell responses in Beninese primigravidae recruited at the beginning of pregnancy and followed up to delivery and beyond...
May 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28526759/il-2-high-tissue-resident-t-cells-in-the-human-liver-sentinels-for-hepatotropic-infection
#11
Laura J Pallett, Jessica Davies, Emily J Colbeck, Francis Robertson, Navjyot Hansi, Nicholas J W Easom, Alice R Burton, Kerstin A Stegmann, Anna Schurich, Leo Swadling, Upkar S Gill, Victoria Male, TuVinh Luong, Amir Gander, Brian R Davidson, Patrick T F Kennedy, Mala K Maini
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well as by primary and metastatic tumors. We have sampled healthy and hepatitis B virus (HBV)-infected human livers to probe for a subset of T cells specialized to overcome local constraints and mediate immunity. We characterize a population of T-bet(lo)Eomes(lo)Blimp-1(hi)Hobit(lo) T cells found within the intrahepatic but not the circulating memory CD8 T cell pool expressing liver-homing/retention markers (CD69(+)CD103(+) CXCR6(+)CXCR3(+))...
May 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28526681/adoptive-transfer-of-phosphoantigen-specific-%C3%AE-%C3%AE-t-cell-subset-attenuates-mycobacterium-tuberculosis-infection-in-nonhuman-primates
#12
Arwa Qaqish, Dan Huang, Crystal Y Chen, Zhuoran Zhang, Richard Wang, Shengpu Li, Enzhuoa Yang, Yang Lu, Michelle H Larsen, William R Jacobs, Lixia Qian, James Frencher, Ling Shen, Zheng W Chen
The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γδ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28524862/antiferromagnetic-cumnas-multi-level-memory-cell-with-microelectronic-compatibility
#13
K Olejník, V Schuler, X Marti, V Novák, Z Kašpar, P Wadley, R P Campion, K W Edmonds, B L Gallagher, J Garces, M Baumgartner, P Gambardella, T Jungwirth
Antiferromagnets offer a unique combination of properties including the radiation and magnetic field hardness, the absence of stray magnetic fields, and the spin-dynamics frequency scale in terahertz. Recent experiments have demonstrated that relativistic spin-orbit torques can provide the means for an efficient electric control of antiferromagnetic moments. Here we show that elementary-shape memory cells fabricated from a single-layer antiferromagnet CuMnAs deposited on a III-V or Si substrate have deterministic multi-level switching characteristics...
May 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28523450/a-review-of-the-clinical-pharmacokinetics-pharmacodynamics-and-immunogenicity-of-vedolizumab
#14
REVIEW
Maria Rosario, Nathanael L Dirks, Catherine Milch, Asit Parikh, Michael Bargfrede, Tim Wyant, Eric Fedyk, Irving Fox
Vedolizumab is a humanized anti-α4β7 integrin monoclonal antibody that selectively blocks trafficking of memory T cells to inflamed gut tissue by inhibiting the α4β7-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) interaction. Approved for treating patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD), vedolizumab is administered as a 300 mg intravenous infusion. Vedolizumab undergoes a rapid, saturable, non-linear, target-mediated elimination process at low concentrations and a slower, linear, non-specific elimination process at higher concentrations...
May 18, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28523432/novel-t-cells-with-improved-in-vivo-anti-tumor-activity-generated-by-rna-electroporation
#15
Xiaojun Liu, Shuguang Jiang, Chongyun Fang, Hua Li, Xuhua Zhang, Fuqin Zhang, Carl H June, Yangbing Zhao
The generation of T cells with maximal anti-tumor activities will significantly impact the field of T-cell-based adoptive immunotherapy. In this report, we found that OKT3/IL-2-stimulated T cells were phenotypically more heterogeneous, with enhanced anti-tumor activity in vitro and when locally administered in a solid tumor mouse model. To further improve the OKT3/IL-2-based T cell manufacturing procedure, we developed a novel T cell stimulation and expansion method in which peripheral blood mononuclear cells were electroporated with mRNA encoding a chimeric membrane protein consisting of a single-chain variable fragment against CD3 and the intracellular domains of CD28 and 4-1BB (OKT3-28BB)...
May 18, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28522585/herpes-simplex-virus-glycoprotein-d-targets-a-specific-dendritic-cell-subset-and-improves-the-performance-of-vaccines-to-human-papillomavirus-associated-tumors
#16
Bruna F M M Porchia, Ana Carolina R Moreno, Rodrigo N Ramos, Mariana O Diniz, Laís Helena T M de Andrade, Daniela S Rosa, José Alexandre M Barbuto, Silvia B Boscardin, Luís Carlos S Ferreira
Cervical cancer is a major public health problem and one of the leading causes of cancer deaths in women. Virtually all cases of cervical cancer, as well as a growing share of anal and head/neck tumors, are associated with human papillomavirus (HPV) infection. Despite the effectiveness, the available prophylactic vaccines do not benefit women with cervical lesions or cancer. Therefore, the search of new immunotherapeutic approaches to treat HPV-induced tumors is still a priority. The present study characterizes a therapeutic antitumor vaccine based on the genetic fusion of the Herpes simplex virus-1 (HSV-1) glycoprotein D (gD) with the E7 oncoprotein from HPV-16 (gDE7)...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28521477/t-cell-immunity-induced-by-a-bivalent-salmonella-based-ceacam6-and-4-1bbl-vaccines-in-a-rat-colorectal-cancer-model
#17
Chunhui Jin, Xiaoqing Duan, Yingying Liu, Jianhong Zhu, Ke Zhang, Yuanting Zhang, Tingting Xia, Yajun Fei, Jianxin Ye
The present study investigated the anti-tumor mechanisms of recombinant non-specific cross-reacting antigen (CEACAM6) and 4-1BB ligand (4-1BBL) Salmonella-based vaccines, and the effect that these vaccinations have on memory T cells and T helper (Th) cell polarization. Colon tumors were induced in rats via 1,2-dimethylhydrazine (DMH) injections. Rats were then treated with injections of attenuated Salmonella typhimurium carrying pIRES-CEACAM6, pIRES-4-1BBL or pIRES-CEACAM6-4-1BBL. In total, 4 vaccine injections, one every other week, were administered during the 8 weeks subsequent to the DMH injection...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520969/cell-mediated-immunity-to-target-the-persistent-human-immunodeficiency-virus-reservoir
#18
James L Riley, Luis J Montaner
Effective clearance of virally infected cells requires the sequential activity of innate and adaptive immunity effectors. In human immunodeficiency virus (HIV) infection, naturally induced cell-mediated immune responses rarely eradicate infection. However, optimized immune responses could potentially be leveraged in HIV cure efforts if epitope escape and lack of sustained effector memory responses were to be addressed. Here we review leading HIV cure strategies that harness cell-mediated control against HIV in stably suppressed antiretroviral-treated subjects...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520966/clonal-expansion-of-human-immunodeficiency-virus-infected-cells-and-human-immunodeficiency-virus-persistence-during-antiretroviral-therapy
#19
James I Mullins, Lisa M Frenkel
The latent HIV-1 reservoir in blood decays very slowly, even during prolonged suppression of viral replication by antiretroviral therapy (ART). Mechanisms for reservoir persistence include replenishment through low-level viral replication, longevity and homeostatic proliferation of memory T cells, and most recently appreciated, clonal expansion of HIV-infected cells. Clonally expanded cells make up a large and increasing fraction of the residual infected cell population on ART, and insertion of HIV proviruses into certain host cellular genes has been associated with this proliferation...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28520183/infected-malnourished-children-displayed-changes-in-early-activation-and-lymphocyte-subpopulations
#20
Oralia Nájera-Medina, Fernando Valencia-Chavarría, Consuelo Cortés-Bejar, Monika Palacios-Martínez, C Paulina Rodríguez-López, María Cristina González-Torres
AIM: Malnutrition and infections cause immunological changes in lymphocyte subpopulations and their functionality. We evaluated the activation capacity of lymphocytes and memory cells in 10 well nourished, seven well nourished infected and eight malnourished infected children before and after treatment. METHODS: All the children were patients in Mexico City and were less than three years of age. The expression of various cluster of differentiation (CD) cells were assessed by flow cytometry: CD45RA (naïve) and CD45RO (memory) antigens on CD4 lymphocytes and CD69 in all lymphocytes...
May 18, 2017: Acta Paediatrica
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