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https://www.readbyqxmd.com/read/28640942/polyfunctional-response-by-immtac-imcgp100-redirected-cd8-and-cd4-t-cells
#1
Caroline Boudousquie, Giovanna Bossi, Jacob M Hurst, Karolina A Rygiel, Bent K Jakobsen, Namir J Hassan
The success of immune system based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilising monoclonal TCRs against cancer (ImmTAC(™) molecules, fusion proteins consisting of a soluble, affinity enhanced TCR and an anti-CD3 scFv Ab) were previously shown to redirect CD8(+) and CD4(+) T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognising a peptide derived from the melanoma-specific protein, gp100, presented by HLA-A*0201) efficiently redirects and activates effector and memory cells from both CD8(+) and CD4(+) repertoires...
June 22, 2017: Immunology
https://www.readbyqxmd.com/read/28640745/the-amino-terminal-subdomain-of-glycoprotein-gc-of-schmallenberg-virus-disulfide-bonding-and-structural-determinants-of-neutralization
#2
Gleyder Roman-Sosa, Axel Karger, Franziska Kraatz, Andrea Aebischer, Kerstin Wernike, Pavlo Maksimov, Christopher H Lillig, Ilona Reimann, Emiliana Brocchi, Markus Keller, Martin Beer
Orthobunyaviruses are enveloped viruses that can cause human and animal diseases. A novel and major member is the Schmallenberg virus (SBV), the etiological agent of an emerging disease of ruminants that has been spreading all over Europe since 2011. The glycoproteins Gn and Gc of orthobunyaviruses mediate the viral entry, and specifically Gc is a major target for the humoral immune response. For example, the N terminal subdomain of the SBV glycoprotein Gc is targeted by neutralizing monoclonal antibodies that recognize conformational epitopes...
June 22, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28636800/molecular-dissection-of-smooth-septate-junctions-understanding-their-roles-in-arthropod-physiology
#3
REVIEW
Mikio Furuse, Yasushi Izumi
Smooth septate junctions (sSJs) are cell-cell junctions that are thought to regulate the paracellular pathway of the intestine and renal system in arthropods. The detailed mechanism of action of sSJs is not well understood, because their molecular organization has remained elusive for a long time. Recently, two sSJ-specific membrane proteins, Ssk and Mesh, were identified by screening monoclonal antibodies raised against sSJ-containing membrane fractions isolated from the silkworm midgut. Furthermore, a genetic screen in Drosophila based on microscopic observation of sSJ formation identified Tsp2A as a novel sSJ-specific membrane protein...
June 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28635644/pd-1-pd-l1-blockade-therapy-for-tumors-with-downregulated-mhc-class-i-expression
#4
REVIEW
Michal Šmahel
The therapy of different advanced-stage malignancies with monoclonal antibodies blocking programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling has had an impressive long-lasting effect in a portion of patients, but in most cases, this therapy was not successful, or a secondary resistance developed. To enhance its efficacy in treated patients, predictive biomarkers are searched for and various combination treatments are intensively investigated. As the downregulation of major histocompatibility complex (MHC) class I molecules is one of the most frequent mechanisms of tumor escape from the host's immunity, it should be considered in PD-1/PD-L1 checkpoint inhibition...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28634122/mapping-the-binding-interface-in-a-non-covalent-size-variant-of-a-monoclonal-antibody-using-native-mass-spectrometry-hydrogen-deuterium-exchange-mass-spectrometry-and-computational-analysis
#5
Yuetian Yan, Hui Wei, Sutjano Jusuf, Stanley R Krystek, Jie Chen, Guodong Chen, Richard T Ludwig, Li Tao, Tapan K Das
Variants of monoclonal antibody containing an extra light chain has been reported in protein products(1-3). Due to potential impact on potency and immunogenicity, it is important to understand the formation mechanism of such variants so that appropriate control strategies can be implemented to assure product quality. In a model monoclonal antibody, we observed a size variant with an extra light chain non-covalently associated with the monomer (later named as "1.2mer"). The interaction between monomer and the extra light chain was characterized by native spray and hydrogen/deuterium exchange mass spectrometry (HDX MS) techniques...
June 17, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28632419/in-vitro-co-expression-of-human-amyloidogenic-immunoglobulin-light-and-heavy-chain-proteins-a-relevant-cell-based-model-of-al-amyloidosis
#6
Elena S Klimtchuk, Tatiana B Prokaeva, Brian H Spencer, Olga Gursky, Lawreen H Connors
Immunoglobulin (Ig) light chain (LC) amyloidosis (AL) is characterized by the overproduction and tissue deposition of monoclonal LC in various organs and tissues. The plasma circulating monoclonal LC is believed to be the precursor of the deposited protein and in vitro studies aimed at understanding AL pathobiology have mainly focused on LC and its variable domain. While 33% of patients have free circulating monoclonal LC, ∼40% feature LC complexed to heavy chain (HC) forming a monoclonal intact Ig; the significance of free vs...
June 20, 2017: Amyloid: the International Journal of Experimental and Clinical Investigation
https://www.readbyqxmd.com/read/28631595/a-32-kda-viral-attachment-protein-of-lymphocystis-disease-virus-lcdv-specifically-interacts-with-a-27-8-kda-cellular-receptor-from-flounder-paralichthys-olivaceus
#7
Ying Zhong, Chenjie Fei, Xiaoqian Tang, Wenbin Zhan, Xiuzhen Sheng
The 27.8 kDa protein in flounder gill (FG) cells was previously proved to be a receptor specific for lymphocystis disease virus (LCDV) entry and infection. In this paper, a 32 kDa viral attachment protein (VAP) of LCDV specifically binding to the 27.8 kDa receptor (27.8R) was found by far-Western blotting coupled with monoclonal antibodies (MAbs) against 27.8R. The 32 kDa protein was confirmed to be encoded by the open reading frame (ORF) 038 gene in LCDV-C, and predicted to contain a putative transmembrane region, multiple N-myristoylation and glycosylation sites and phosphorylation motifs...
June 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28631593/a-denv-2-type-specific-monoclonal-antibody-binds-to-the-denv-complex-reactive-antigenic-site-on-envelope-protein-domain-3
#8
Vanessa V Sarathy, Trevor J Pitcher, Gregory D Gromowski, John T Roehrig, Alan D T Barrett
The Dengue virus (DENV) envelope (E) protein is the major component of the viral surface and is structurally subdivided into three domains, ED1, ED2 and ED3. ED3 elicits potent neutralizing antibodies and contains two major antigenic sites: the DENV-type-specific and DENV-complex-reactive antigenic sites. Each site is composed of a limited subset of residues that are required for monoclonal antibody (mAb) binding. Here we show that DENV-2-type-specific mAb 9A3D-8 utilizes the functionally critical residues K307, V308, K310, I312, P332, L387, L389 and N390 for ED3 binding...
June 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28631095/decorin-gene-upregulation-mediated-by-an-adeno-associated-virus-vector-increases-intratumoral-uptake-of-nab-paclitaxel-in-neuroblastoma-via-inhibition-of-stabilin-1
#9
Zijun Zhen, Kaibin Yang, Litong Ye, Zhiyao You, Rirong Chen, Ying Liu
The availability of effective medication for the treatment of refractory or recurrent neuroblastoma remains limited. This study sought to investigate the effects of increased decorin (DCN) expression on the intratumoral uptake of nab-paclitaxel as a potential novel approach to NB. Correlation between the clinical characteristics of neuroblastoma and the expression of DCN, secreted protein acidic and rich in cysteine (SPARC) and stabilin-1 was evaluated. The anticancer effect of recombinant adeno-associated virus-DCN (rAAV-DCN) was assessed in vivo and in vitro...
June 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28630381/antibody-response-to-human-extracellular-her2-subdomain-proteins-in-mice
#10
Fateme Sadri-Ardalani, Moslem Ahmadi, Azam Hemmati, Shaghayegh Emami, Samira Farid, Mohammad Mehdi Amiri, Mahmood Jeddi-Tehrani, Mahdi Shabani, Fazel Shokri
BACKGROUND: In addition to passive immunotherapy using anti-HER2 monoclonal antibodies, active immunotherapy via HER2 targeting is an interesting approach to inducing specific anti-tumor immune responses. We have recently reported the immunogenicity of HER2 subdomains following DNA immunization and HER2 protein boosting. In the present study, we evaluated the immunogenicity of different HER2 extracellular subdomains for the induction of anti-HER2 antibody response in BALB/c mice. OBJECTIVE: To investigate and characterize antibody responses to human recombinant proteins of HER2 extracellular subdomains in immunized mice...
June 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28629465/natural-igm-antibodies-that-bind-neoepitopes-exposed-as-a-result-of-spinal-cord-injury-drive-secondary-injury-by-activating-complement
#11
Aarti Narang, Fei Qiao, Carl Atkinson, Hong Zhu, Xiaofeng Yang, Liudmila Kulik, V Michael Holers, Stephen Tomlinson
BACKGROUND: Natural IgM antibodies (Abs) function as innate immune sensors of injury via recognition of neoepitopes expressed on damaged cells, although how this recognition systems function following spinal cord injury (SCI) exposes various neoepitopes and their precise nature remains largely unknown. Here, we investigated the role of two natural IgM monoclonal Abs (mAbs), B4 and C2, that recognize post-ischemic neoepitopes following ischemia and reperfusion in other tissues. METHODS: Identification of post-SCI expressed neoepitopes was examined using previously characterized monoclonal Abs (B4 and C2 mAbs)...
June 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28629383/epitope-mapping-and-characterization-of-a-novel-nsp10-specific-monoclonal-antibody-that-differentiates-genotype-2-prrsv-from-genotype-1-prrsv
#12
Zhibang Zhang, Xuexia Wen, Jianguo Dong, Xinna Ge, Lei Zhou, Hanchun Yang, Xin Guo
BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV), the causative agent of PRRS, has two distinct and highly diverse genotypes (genotype 1 and genotype 2) in the field. Accurate diagnosis and differentiation of the two genotypes of PRRSV are critical to the effective prevention and control of PRRS. The non-structural protein 10 (Nsp10) plays a vital role in viral replication and is one of the most conserved proteins of PRRSV, thus constituting a good candidate for PRRSV diagnosis...
June 19, 2017: Virology Journal
https://www.readbyqxmd.com/read/28628829/ectromelia-virus-accumulates-less-double-stranded-rna-compared-to-vaccinia-virus-in-bs-c-1-cells
#13
Tiffany R Frey, Michael H Lehmann, Colton M Ryan, Marie C Pizzorno, Gerd Sutter, Adam R Hersperger
Most orthopoxviruses, including vaccinia virus (VACV), contain genes in the E3L and K3L families. The protein products of these genes have been shown to combat PKR, a host defense pathway. Interestingly, ectromelia virus (ECTV) contains an E3L ortholog but does not possess an intact K3L gene. Here, we gained insight into how ECTV can still efficiently evade PKR despite lacking K3L. Relative to VACV, we found that ECTV-infected BS-C-1 cells accumulated considerably less double-stranded (ds) RNA, which was due to lower mRNA levels and less transcriptional read-through of some genes by ECTV...
June 16, 2017: Virology
https://www.readbyqxmd.com/read/28627827/a-case-of-waldenstrom-macroglobulinemia-with-temporary-appearance-of-7s-igm-half-molecule
#14
Mayumi Imoto, Koji Yoshida, Yasuhiro Maeda, Ken-Ichi Nakae, Masatoshi Kudo, Ikunosuke Sakurabayashi, Toshiyuki Yamada, Toshinori Kamisako
BACKGROUND: We encountered a rare case of Waldenstrom macroglobulinemia with temporary appearance of 7S IgM half molecule and with monoclonal proteins binding to agarose gel. METHODS: The patient's serum and urine were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The N-terminal amino acid sequences of the IgM with abnormal mass (68 kDa) were determined and compared with those of known immunoglobulin. RESULTS: The 68 kDa IgM consisted of a defective μ chain (36 kDa) and an intact κ chain...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28627716/a-cherry-seed-derived-spice-mahleb-is-recognized-by-anti-almond-antibodies-including-almond-allergic-patient-ige
#15
Kyle A Noble, Changqi Liu, Shridhar K Sathe, Kenneth H Roux
There are a number of examples of immunologic cross-reactivity elicited by pollens, fruits, seeds, and nuts of closely related plant species. Such cross-reactivity is of particular concern for patients with food allergies. In this report, we investigated a spice (mahleb) that is prepared from the kernel of the St. Lucie cherry, Prunus mahaleb, for cross-reactivity with almond (Prunus dulcis), using enzyme-linked immunosorbent assay (ELISA) and Western blot. Almond and mahleb are members of the same genus. Cross-reactivity between the mahleb and almond was demonstrated by reaction of cherry and almond kernel protein extracts with antibodies raised against almond proteins...
June 19, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28627280/the-targeting-effect-of-hm2e8b-nctd-liposomes-on-b-lineage-leukemia-stem-cells-is-associated-with-the-hlf-slug-axis
#16
Jingying Zhang, Diyin Shen, Min Jia, Haizhao Zhao, Yongmin Tang
To identify an agent with specific activity against B-lineage leukemia stem cells (B-LSCs), we generated norcantharidin (NCTD)-encapsulated liposomes modified with a novel humanized anti-human CD19 monoclonal antibody, Hm2E8b (Hm2E8b-NCTD-liposomes). These liposomes were specially designed to recognize and kill B-LSCs in vitro, and to decrease non-specific cytotoxicity to untargeted cells. Hm2E8b-NCTD-liposomes selectively ablated B-LSCs through targeting hepatic leukemia factor (HLF), which is implicated in hematopoietic stem cell regulation and is overexpressed in LSCs...
June 19, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28626947/pharmacokinetic-study-of-bortezomib-administered-intravenously-in-taiwanese-patients-with-multiple-myeloma
#17
Shang-Yi Huang, Cheng-Shyong Chang, Ta-Chih Liu, Po-Nan Wang, Su-Peng Yeh, Ching-Liang Ho, Ming-Chung Kuo, Hsuan-Yu Lin, Jan de Jong, Jia-Yi Chen, Ya-Wen Yang
This phase 4, single-arm, non-randomized, open-label, post approval commitment study evaluated the pharmacokinetics and safety of bortezomib in Taiwanese patients with multiple myeloma. Patients (≥20 years) with measurable secretory multiple myeloma (serum monoclonal IgG ≥10, IgA/IgE ≥5, IgD ≥0.5 g/L, IgM present [regardless of level], and urine M protein of ≥200 mg/24 h) received intravenous bortezomib 1.3 mg/m(2) , twice weekly for 2 weeks, followed by a 10-day resting phase (days 12 to 21)...
June 19, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28624430/comparative-assessment-of-immune-complex-mediated-hypersensitivity-reactions-with-biotherapeutics-in-the-non-human-primate-critical-parameters-safety-and-lessons-for-future-studies
#18
Sven Kronenberg, Elisabeth Husar, Christine Schubert, Christian Freichel, Thomas Emrich, Martin Lechmann, Anna Maria Giusti, Franziska Regenass
With the emergence of novel biotherapeutic formats and immunostimulatory biotherapeutics in cancer immunotherapy, an understanding of immune-complex (IC) mediated hypersensitivity reactions in toxicology studies - and their differentiation from pharmacology - remains key to the preclinical evaluation of these drugs. In this review we provide an in-depth evaluation and comparison of case examples where IC-mediated hypersensitivity reactions were observed in cynomolgus monkeys. We provide details of the parameters evaluated in each study to substantiate and guide the interpretation of these findings...
June 15, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28621534/construction-of-an-immunized-rabbit-phage-display-library-for-selecting-high-activity-of-against-bacillus-thuringiensis-cry1f-toxin-single-chain-antibodies
#19
Chongxin Xu, Cunzheng Zhang, Jianfeng Zhong, Hui Hu, Shimin Luo, Xiaoqin Liu, Xiao Zhang, Yuan Liu, Xianjin Liu
In the present study, a Cry1F-immunized rabbit phage display library (6.96×108) was constructed for selecting high activity of anti-Cry1F toxin single-chain antibody (scFv) by bio-panning. Total 16 positive monoclonal phage scFvs were obtained after 4 rounds panning which identified by enzyme-linked immunoassay (ELISA), PCR and DNA sequencing. The most positive phage scFv (named RF4) was expressed in E.coli.HB2151 and the purified soluble protein approximate 30 kDa with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)...
June 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28619527/expression-of-full-length-her2-protein-in-sf9-insect-cells-and-its-presentation-on-the-surface-of-budded-virus-like-particles
#20
Lisa Nika, Jakob Wallner, Dieter Palmberger, Krisztina Koczka, Karola Vorauer-Uhl, Reingard Grabherr
Biomarkers of cancer are often glycosylated membrane receptor proteins present on the cellular surface. In order to develop new antibodies for cancer diagnostics or treatment, it is a main pre-requisite that these target proteins are available in a native conformation. However, membrane receptor proteins are notoriously difficult to produce due to their hydrophobic nature and complex architecture. Here, we used the baculovirus-insect cell expression system to produce budded virus-like particles (VLPs) as the scaffold for the presentation of complex membrane proteins...
June 12, 2017: Protein Expression and Purification
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