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https://www.readbyqxmd.com/read/29166592/hiv-envelope-glycoform-heterogeneity-and-localized-diversity-govern-the-initiation-and-maturation-of-a-v2-apex-broadly-neutralizing-antibody-lineage
#1
Elise Landais, Ben Murrell, Bryan Briney, Sasha Murrell, Kimmo Rantalainen, Zachary T Berndsen, Alejandra Ramos, Lalinda Wickramasinghe, Melissa Laird Smith, Kemal Eren, Natalia de Val, Mengyu Wu, Audrey Cappelletti, Jeffrey Umotoy, Yolanda Lie, Terri Wrin, Paul Algate, Po-Ying Chan-Hui, Etienne Karita, Andrew B Ward, Ian A Wilson, Dennis R Burton, Davey Smith, Sergei L Kosakovsky Pond, Pascal Poignard
Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166012/the-use-of-fluoroproline-in-muc1-antigen-enables-efficient-detection-of-antibodies-in-patients-with-prostate-cancer
#2
Víctor Jesús Somovilla, Iris Alicia Bermejo, Inês S Albuquerque, Nuria Martínez-Sáez, Jorge Castro-López, Fayna Garcia Martin, Ismael Compañón, Hiroshi Hinou, Shin-Ichiro Nishimura, Jesús Jiménez-Barbero, Juan Luis Asensio, Alberto Avenoza, Jesús H Busto, Ramon Hurtado-Guerrero, Jesús M Peregrina, Gonçalo J L Bernardes, Francisco Corzana
A structure-based design of a new generation tumor-associated glycopeptides with improved affinity against two anti-MUC1 antibodies is described. These unique antigens feature a fluorinated proline residue, such as a (4S)-4-fluoro-L-proline or 4,4-difluoroproline, at the most immunogenic domain. Binding assays using bio-layer interferometry reveal 3-fold to 10-fold affinity improvement with respect to the natural (glyco)peptides. According to X-ray crystallography and MD simulations, the fluorinated residues stabilize the antigen-antibody complex by enhancing key CH/π interactions...
November 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29164803/preclinical-evaluation-and-optimization-of-a-cell-therapy-using-human-cord-blood-derived-endothelial-colony-forming-cells-for-ischemic-retinopathies
#3
Emma Reid, Jasenka Guduric-Fuchs, Christina L O'Neill, Lynsey-Dawn Allen, Sarah E J Chambers, Alan W Stitt, Reinhold J Medina
Cell therapy using endothelial progenitors holds promise for vascular repair in ischemic retinopathies. Using a well-defined subpopulation of human cord blood-derived endothelial progenitors known as endothelial colony-forming cells (ECFCs), we have evaluated essential requirements for further development of this cell therapy targeting the ischemic retina, including dose response, delivery route, and toxicity. First, to evaluate therapeutic efficacy relating to cell dose, ECFCs were injected into the vitreous of mice with oxygen-induced retinopathy...
November 22, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29164593/immune-correlates-of-clinical-outcome-in-melanoma
#4
REVIEW
Graham Pawelec
Melanoma has long been recognized as a potentially immunogenic tumour, but only recently has it become clear that the reason for this resides in its many UV-induced mutations and expression of multiple autoantigens which can be targeted by the immune system. The first successful applications of immune-based treatments included passive immunotherapy using high-dose IL-2 and/or adoptive transfer of NK-cells, as well as active immunotherapy using whole cell-derived or peptide vaccines. In the intervening decades, it has become clear that these approaches can lead to durable responses in stage III/IV melanoma, and even to functional cures - but only in a vanishingly small fraction of patients...
November 21, 2017: Immunology
https://www.readbyqxmd.com/read/29164070/generation-of-an-attenuated-tiantan-vaccinia-virus-strain-by-deletion-of-multiple-genes
#5
Yiquan Li, Yilong Zhu, Shuang Chen, Wenjie Li, Xunzhe Yin, Shanzhi Li, Pengpeng Xiao, Jicheng Han, Xiao Li, Lili Sun, Ningyi Jin
An attenuated vaccinia virus-MVTTEAB-was constructed by deletion of non-essential gene segments related to the immunomodulatory and virulence functions of the vaccinia virus Tiantan strain (VVTT). The shuttle plasmids pTC-EGFP, pTE-EGFP, pTA35-EGFP, pTB-EGFP, and pTA66-EGFP were constructed and combined with the early and late strong promoter pE/L and EGFP as an exogenous selectable marker. Then, through the homologous recombination technology and Cre/loxP system, the following gene fragments were gradually knocked out one by one: TC7L-TK2L, TE3L, TA35R, TB13R, and TA66R...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29164053/synergistic-protective-activity-of-tumor-specific-epitopes-engineered-in-bacterial-outer-membrane-vesicles
#6
Alberto Grandi, Michele Tomasi, Ilaria Zanella, Luisa Ganfini, Elena Caproni, Laura Fantappiè, Carmela Irene, Luca Frattini, Samine J Isaac, Enrico König, Francesca Zerbini, Simona Tavarini, Chiara Sammicheli, Fabiola Giusti, Ilaria Ferlenghi, Matteo Parri, Guido Grandi
Introduction: Bacterial outer membrane vesicles (OMVs) are naturally produced by all Gram-negative bacteria and, thanks to their plasticity and unique adjuvanticity, are emerging as an attractive vaccine platform. To test the applicability of OMVs in cancer immunotherapy, we decorated them with either one or two protective epitopes present in the B16F10EGFRvIII cell line and tested the protective activity of OMV immunization in C57BL/6 mice challenged with B16F10EGFRvIII. Materials and methods: The 14 amino acid B cell epitope of human epidermal growth factor receptor variant III (EGFRvIII) and the mutation-derived CD4+ T cell neo-epitope of kif18b gene (B16-M30) were used to decorate OMVs either alone or in combination...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29163540/local-high-dose-radiotherapy-induces-systemic-immunomodulating-effects-of-potential-therapeutic-relevance-in-oligometastatic-breast-cancer
#7
Elena Muraro, Carlo Furlan, Michele Avanzo, Debora Martorelli, Elisa Comaro, Aurora Rizzo, Damiana A Fae', Massimiliano Berretta, Loredana Militello, Alessandro Del Conte, Simon Spazzapan, Riccardo Dolcetti, Marco Trovo'
Local irradiation of cancer through radiotherapy can induce spontaneous regression of non-directly irradiated lesions, suggesting the involvement of systemic antitumor immune responses. In oligometastatic breast cancer (BC) patients, the use of stereotactic body radiotherapy (SBRT) favors the local control of treated lesions and may contribute to break local tolerance and release tumor-associated antigens (TAAs), improving host antitumor immunity. We performed a detailed immunomonitoring of BC patients undergoing SBRT to verify its ability to "switch on" the anti-tumor immunity both systemically, in peripheral blood, and locally, employing in vitro BC models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163532/biodistribution-and-immunogenicity-of-allogeneic-mesenchymal-stem-cells-in-a-rat-model-of-intraarticular-chondrocyte-xenotransplantation
#8
Maribel Marquina, Javier A Collado, Magdiel Pérez-Cruz, Pablo Fernández-Pernas, Juan Fafián-Labora, Francisco J Blanco, Rafael Máñez, María C Arufe, Cristina Costa
Xenogeneic chondrocytes and allogeneic mesenchymal stem cells (MSC) are considered a potential source of cells for articular cartilage repair. We here assessed the immune response triggered by xenogeneic chondrocytes when injected intraarticularly, as well as the immunoregulatory effect of allogeneic bone marrow-derived MSC after systemic administration. To this end, a discordant xenotransplantation model was established by injecting three million porcine articular chondrocytes (PAC) into the femorotibial joint of Lewis rats and monitoring the immune response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163515/nanobody-based-delivery-systems-for-diagnosis-and-targeted-tumor-therapy
#9
REVIEW
Yaozhong Hu, Changxiao Liu, Serge Muyldermans
The development of innovative targeted therapeutic approaches are expected to surpass the efficacy of current forms of treatments and cause less damage to healthy cells surrounding the tumor site. Since the first development of targeting agents from hybridoma's, monoclonal antibodies (mAbs) have been employed to inhibit tumor growth and proliferation directly or to deliver effector molecules to tumor cells. However, the full potential of such a delivery strategy is hampered by the size of mAbs, which will obstruct the targeted delivery system to access the tumor tissue...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163502/regulating-immunogenicity-and-tolerogenicity-of-bone-marrow-derived-dendritic-cells-through-modulation-of-cell-surface-glycosylation-by-dexamethasone-treatment
#10
Kevin Lynch, Oliver Treacy, Jared Q Gerlach, Heidi Annuk, Paul Lohan, Joana Cabral, Lokesh Joshi, Aideen E Ryan, Thomas Ritter
Dendritic cellular therapies and dendritic cell vaccines show promise for the treatment of autoimmune diseases, the prolongation of graft survival in transplantation, and in educating the immune system to fight cancers. Cell surface glycosylation plays a crucial role in the cell-cell interaction, uptake of antigens, migration, and homing of DCs. Glycosylation is known to change with environment and the functional state of DCs. Tolerogenic DCs (tDCs) are commonly generated using corticosteroids including dexamethasone, however, to date, little is known on how corticosteroid treatment alters glycosylation and what functional consequences this may have...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29162646/nkg2d-dependent-anti-tumor-effects-of-chemotherapy-and-radiotherapy-against-glioblastoma
#11
Tobias Weiss, Hannah Schneider, Manuela Silginer, Alexander Steinle, Martin N Pruschy, Bojan Polic, Michael Weller, Patrick Roth
PURPOSE: NKG2D is a potent activating immune cell receptor and glioma cells express the cognate ligands (NKG2DL). These ligands are inducible by cellular stress and temozolomide (TMZ) or irradiation (IR), the standard treatment of glioblastoma, could affect their expression. However, a role of NKG2DL for the efficacy of TMZ and IR has never been addressed. EXPERIMENTAL DESIGN: We assessed the effect of TMZ and IR on NKG2DL in vitro and in vivo in a variety of murine and human glioblastoma models including glioma-initiating cells and a cohort of paired glioblastoma samples from patients before and after therapy...
November 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29161775/the-influence-of-different-peptide-combinations-to-increase-the-immunogenicity-of-the-gonadotrophin-releasing-hormone-vaccine-for-prostate-cancer-treatment
#12
Franklin Fuentes Aguilar, Jesús Junco Barranco, Lesvia Calzada Aguilera, Eddy Bover Fuentes, Jose André Serradelo Leal, Eduardo Hernández López, Eulogio Pimentel Vázquez, Roberto Basulto Baker, Osvaldo Reyes Acosta, Hilda Garay Pérez, Gerardo Guillén Nieto
Purpose: Therapeutic vaccines, specifically the Gonadotrophin Releasing Hormone (GnRH) vaccine, are considered an additional therapeutic option for advanced stage prostate cancer. Our work showed amplification of the immune response when combining two peptides with and without the Very Small Size Proteoliposomes (VSSP). VSSP is a potent adjuvant for dendritic cells activation and Th1 differentiation. as enhanced immune response. Methods: The test was carried out in Copenhagen rats as animal model...
November 2017: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/29160512/evaluation-of-the-immunogenicity-of-schistosoma-mansoni-egg-surface
#13
Renata Russo Frasca Candido, Timothy Guy St Pierre, Malcolm Kenneth Jones, Carlos Graeff-Teixeira
INTRODUCTION: Immunogenicity of Schistosoma mansoni egg surface was examined to determine whether intact eggshells have lower antigenicity than ruptured eggs. METHODS: Swiss Webster mice were inoculated with intact or ultrasonicated S. mansoni eggs isolated from infected human feces. Mice were separated into four groups of six animals each and immunizations were performed approximately every 20 days during a 60-day period. Groups 1-4 were administered with saline solution, sonicated eggs with Freund's adjuvant, sonicated eggs without Freund's adjuvant, and intact eggs, respectively...
September 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/29159802/adenovirus-vector-based-prime-boost-vaccination-via-heterologous-routes-induces-cervicovaginal-cd8-t-cell-responses-against-hpv16-oncoproteins
#14
Nicolas Çuburu, Selina Khan, Cynthia D Thompson, Rina Kim, Jort Vellinga, Roland Zahn, Douglas R Lowy, Gert Scheper, John T Schiller
Recent advances in immunotherapy against cancer underscore the importance of T lymphocytes and tumor microenvironment, but few vaccines targeting cancer have been approved likely due in part to the dearth of common tumor antigens, insufficient immunogenicity and the evolution of immune evasion mechanisms during the progression to malignancy. Human papillomaviruses (HPV) are the primary etiologic agents of cervical cancer and progression from persistent HPV-infection to cervical intraepithelial lesions and eventually cancer requires persistent expression of the oncoproteins E6 and E7...
November 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29159320/immunogenicity-and-persistence-of-the-13-valent-pneumococcal-conjugate-vaccine-pcv13-in-patients-with-untreated-smoldering-multiple-myeloma-smm-a-pilot-study
#15
Mathilde Bahuaud, Hélène Bodilis, Marion Malphettes, Anaïs Maugard Landre, Caroline Matondo, Didier Bouscary, Frédéric Batteux, Odile Launay, Jean-Paul Fermand
Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder that frequently progress to multiple myeloma (MM), a disease at high risk of pneumococcal infections. Moreover, if the polysaccharide vaccine is poorly immunogenic in MM, the 13-valent conjugated vaccine has never been tested in clonal plasma cell disorders. We evaluated its immunogenicity for 7 serotypes in 20 patients ≥ 50 years of age with smoldering multiple myeloma (SMM) pre and post routine-vaccination with PCV13. Concentrations of IgG specific for 7 serotypes were measured at baseline, 1, 6, and 12 months after vaccination by standardized ELISA and an Opsonophagocytic Assay (OPA)...
November 2017: Heliyon
https://www.readbyqxmd.com/read/29159187/the-role-of-costimulation-blockade-in-solid-organ-and-islet-xenotransplantation
#16
REVIEW
Kannan P Samy, James R Butler, Ping Li, David K C Cooper, Burcin Ekser
Pig-to-human xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advances have led to highly efficient and targeted genomic editing, drastically altering the playing field towards rapid production of less immunogenic porcine tissues and even the discussion of human xenotransplantation trials...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29158984/virus-like-particles-as-a-platform-for-cancer-vaccine-development
#17
Hui Kian Ong, Wen Siang Tan, Kok Lian Ho
Cancers have killed millions of people in human history and are still posing a serious health problem worldwide. Therefore, there is an urgent need for developing preventive and therapeutic cancer vaccines. Among various cancer vaccine development platforms, virus-like particles (VLPs) offer several advantages. VLPs are multimeric nanostructures with morphology resembling that of native viruses and are mainly composed of surface structural proteins of viruses but are devoid of viral genetic materials rendering them neither infective nor replicative...
2017: PeerJ
https://www.readbyqxmd.com/read/29158574/immunogenicity-and-loss-of-response-to-tnf-inhibitors-implications-for-rheumatoid-arthritis-treatment
#18
REVIEW
Joachim R Kalden, Hendrik Schulze-Koops
The availability of monoclonal antibodies has revolutionized the treatment of an increasingly broad spectrum of diseases. Inflammatory diseases are among those most widely treated with protein-based therapeutics, termed biologics. Following the first large-scale clinical trials with monoclonal antibodies performed in the 1990s by rheumatologists and clinical immunologists, the approval of these agents for use in daily clinical practice led to substantial progress in the treatment of rheumatic diseases. Despite this progress, however, only a proportion of patients achieve a long-term clinical response...
November 21, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/29158362/cd38-bispecific-antibody-pretargeted-radioimmunotherapy-for-multiple-myeloma-and-other-b-cell-malignancies
#19
Damian J Green, Shyril O'Steen, Yukang Lin, Melilssa L Comstock, Aimee L Kenoyer, Donald K Hamlin, D Scott Wilbur, Darrell R Fisher, Margaret Nartea, Mark D Hylarides, Ajay K Gopal, Theodore A Gooley, Johnnie J Orozco, Brian G Till, Kelly D Orcutt, K Dane Wittrup, Oliver W Press
Pretargeted radioimmunotherapy (PRIT) has demonstrated remarkable efficacy targeting tumor antigens, but immunogenicity and endogenous biotin blocking may limit clinical translation. We describe a new PRIT approach for the treatment of Multiple Myeloma (MM) and other B cell malignancies, for which we developed an anti-CD38 bispecific fusion protein that eliminates endogenous biotin interference and immunogenic elements. In murine xenograft models of MM and non-Hodgkin lymphoma (NHL), the CD38 bispecific construct demonstrated excellent blood clearance and tumor targeting...
November 20, 2017: Blood
https://www.readbyqxmd.com/read/29158190/prevalence-of-microsatellite-instability-in-intraductal-papillary-mucinous-neoplasms-of-the-pancreas
#20
R M Lupinacci, A Goloudina, O Buhard, J B Bachet, R Maréchal, P Demetter, J Cros, A Bardier-Dupas, A Collura, P Cervera, A Scriva, S Dumont, P Hammel, A Sauvanet, C Louvet, J-R Delpéro, F Paye, J-C Vaillant, T André, J Closset, J-F Emile, J-L Van Laethem, V Jonchère, I Abd Alsamad, M Antoine, A Rodenas, J F Fléjou, N Dusetti, J Iovanna, A Duval, M Svrcek
Microsatellite instability (MSI) due to mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical analyses of a 445 PDAC specimens, collected from consecutive patients at multiple centers, to identify those with dMMR, based on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2. We detected dMMR in 1...
November 17, 2017: Gastroenterology
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