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Neoepitopes

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https://www.readbyqxmd.com/read/29769288/targeted-complement-inhibition-salvages-stressed-neurons-and-inhibits-neuroinflammation-after-stroke-in-mice
#1
Ali Alawieh, E Farris Langley, Stephen Tomlinson
Ischemic stroke results from the interruption of blood flow to the brain resulting in long-term motor and cognitive neurological deficits, and it is a leading cause of death and disability. Current interventions focus on the restoration of blood flow to limit neuronal death, but these treatments have a therapeutic window of only a few hours and do not address post-stroke cerebral inflammation. The complement system, a component of the innate immune system, is activated by natural immunoglobulin M (IgM) antibodies that recognize neoepitopes expressed in the brain after ischemic stroke...
May 16, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29731959/identification-of-neoepitopes-recognized-by-tumor-infiltrating-lymphocytes-tils-from-patients-with-glioma
#2
Davide Valentini, Martin Rao, Qingda Meng, Anna von Landenberg, Jiri Bartek, Georges Sinclair, Georgia Paraschoudi, Elke Jäger, Inti Harvey-Peredo, Ernest Dodoo, Markus Maeurer
Neoepitope-specific T-cell responses have been shown to induce durable clinical responses in patients with advanced cancers. We explored the recognition patterns of tumor-infiltrating T lymphocytes (TILs) from patients with glioblastoma multiforme (GBM), the most fatal form of tumors of the central nervous system. Whole-genome sequencing was used for generating DNA sequences representing the entire spectrum of 'private' somatic mutations in GBM tumors from five patients, followed by 15-mer peptide prediction and subsequent peptide synthesis...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29720262/upper-zone-of-growth-plate-and-cartilage-matrix-associated-protein-protects-cartilage-during-inflammatory-arthritis
#3
Fritz Seuffert, Daniela Weidner, Wolfgang Baum, Georg Schett, Michael Stock
BACKGROUND: ADAMTS aggrecanases play a major role in cartilage degeneration during degenerative and inflammatory arthritis. The cartilage-specific secreted protein Upper zone of growth plate and cartilage matrix associated protein (Ucma) has been shown to block ADAMTS-triggered aggrecanolysis in experimental osteoarthritis. Here we aimed to investigate whether and how Ucma may affect cartilage destruction and osteophyte formation in the context of inflammatory arthritis. METHODS: Ucma-ADAMTS5 protein interactions were studied using slot blot and solid phase binding assays...
May 2, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29702061/aggrecanase-degradation-of-type-iii-collagen-is-associated-with-clinical-knee-pain
#4
A C Bay-Jensen, C F Kjelgaard-Petersen, K K Petersen, L Arendt-Nielsen, H L Quasnichka, A Mobasheri, M A Karsdal, D J Leeming
There is a lack of biochemical markers for non-invasive and objective assessment of symptomatic osteoarthritis (OA). Aggrecanase activity has been shown to be associated with joint deterioration and symptomatic disease through the degradation of extracellular matrix proteins, such as type III collagen. Our study aimed to identify and develop a novel biomarker by measuring an aggrecanase-mediated type III collagen neoepitope, and correlate levels of this biomarker with OA joint pain. Mass spectrometric analysis of purified type III collagen, degraded by the aggrecanase A Disintigrin and Metalloproteinase with Thrombospondin motif (ADAMTS), revealed a fragment generated by ADAMTS-1, -4 and -8...
April 24, 2018: Clinical Biochemistry
https://www.readbyqxmd.com/read/29643231/personalized-cancer-vaccine-effectively-mobilizes-antitumor-t-cell-immunity-in-ovarian-cancer
#5
Janos L Tanyi, Sara Bobisse, Eran Ophir, Sandra Tuyaerts, Annalisa Roberti, Raphael Genolet, Petra Baumgartner, Brian J Stevenson, Christian Iseli, Denarda Dangaj, Brian Czerniecki, Aikaterini Semilietof, Julien Racle, Alexandra Michel, Ioannis Xenarios, Cheryl Chiang, Dimitri S Monos, Drew A Torigian, Harvey L Nisenbaum, Olivier Michielin, Carl H June, Bruce L Levine, Daniel J Powell, David Gfeller, Rosemarie Mick, Urania Dafni, Vincent Zoete, Alexandre Harari, George Coukos, Lana E Kandalaft
We conducted a pilot clinical trial testing a personalized vaccine generated by autologous dendritic cells (DCs) pulsed with oxidized autologous whole-tumor cell lysate (OCDC), which was injected intranodally in platinum-treated, immunotherapy-naïve, recurrent ovarian cancer patients. OCDC was administered alone (cohort 1, n = 5), in combination with bevacizumab (cohort 2, n = 10), or bevacizumab plus low-dose intravenous cyclophosphamide (cohort 3, n = 10) until disease progression or vaccine exhaustion. A total of 392 vaccine doses were administered without serious adverse events...
April 11, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29643180/structural-control-of-caspase-generated-glutamyl-trna-synthetase-by-appended-noncatalytic-whep-domains
#6
Dalia Halawani, Valentin Gogonea, Joseph A DiDonato, Vitaliy Pipich, Peng Yao, Arnab China, Celalettin Topbas, Kommireddy Vasu, Abul Arif, Stanley L Hazen, Paul L Fox
Aminoacyl-tRNA synthetases are ubiquitous, evolutionarily conserved enzymes catalyzing the conjugation of amino acids onto cognate tRNAs. During eukaryotic evolution, tRNA synthetases have been the targets of persistent structural modifications. These modifications can be additive, as in the evolutionary acquisition of noncatalytic domains, or subtractive, as in the generation of truncated variants through regulated mechanisms such as proteolytic processing, alternative splicing, or coding region polyadenylation...
April 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29615349/assessment-of-extracellular-matrix-related-biomarkers-in-patients-with-lower-extremity-artery-disease
#7
Anna Hernández-Aguilera, Signe Holm Nielsen, Cristina Bonache, Salvador Fernández-Arroyo, Vicente Martín-Paredero, Montserrat Fibla, Morten A Karsdal, Federica Genovese, Javier A Menendez, Jordi Camps, Jorge Joven
BACKGROUND: The prevalence of lower extremity artery disease (LEAD) is high (20%-25%) in the population older than 65 years, but patients are seldom identified until the disease is advanced. Circulating markers of disease activity might provide patients with a key opportunity for timely treatment. We tested the hypothesis that measuring blood-specific fragments generated during degradation of the extracellular matrix (ECM) could provide further insight into the pathophysiologic mechanism of arterial remodeling...
March 31, 2018: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/29594595/vaccine-strategies-in-gliomas
#8
REVIEW
Michael Platten, Lukas Bunse, Dennis Riehl, Theresa Bunse, Katharina Ochs, Wolfgang Wick
PURPOSE OF REVIEW: To discuss the current state of glioma vaccine development and highlight the challenges associated with clinical implementation of these approaches. RECENT FINDINGS: Vaccination strategies against gliomas have matured considerably during the past years, although proof-of efficacy from controlled clinical trials is still lacking. Advances in antigen discovery, including the definition of neoepitopes including epidermal growth factor receptor variant III (EGFRvIII), isocitrate dehydrogenase (IDH)1R132H and Histone (H)3...
March 28, 2018: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29582551/bacterial-killing-by-platelets-making-sense-of-h-it
#9
M F Hoylaerts, T Vanassche, P Verhamme
No abstract text is available yet for this article.
March 27, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29567706/personalized-vaccines-for-cancer-immunotherapy
#10
REVIEW
Ugur Sahin, Özlem Türeci
Cancer is characterized by an accumulation of genetic alterations. Somatic mutations can generate cancer-specific neoepitopes that are recognized by autologous T cells as foreign and constitute ideal cancer vaccine targets. Every tumor has its own unique composition of mutations, with only a small fraction shared between patients. Technological advances in genomics, data science, and cancer immunotherapy now enable the rapid mapping of the mutations within a genome, rational selection of vaccine targets, and on-demand production of a therapy customized to a patient's individual tumor...
March 23, 2018: Science
https://www.readbyqxmd.com/read/29541393/effective-screening-of-t-cells-recognizing-neoantigens-and-construction-of-t-cell-receptor-engineered-t-cells
#11
Taigo Kato, Tatsuo Matsuda, Yuji Ikeda, Jae-Hyun Park, Matthias Leisegang, Sachiko Yoshimura, Tetsuro Hikichi, Makiko Harada, Makda Zewde, Sho Sato, Kosei Hasegawa, Kazuma Kiyotani, Yusuke Nakamura
Neoantigens are the main targets of tumor-specific T cells reactivated by immune checkpoint-blocking antibodies or when using tumor-infiltrating T cells for adoptive therapy. While cancers often accumulate hundreds of mutations and harbor several immunogenic neoantigens, the repertoire of mutation-specific T cells in patients might be restricted. To bypass suboptimal conditions, which impede the reactivation of existing T cells or the priming of neoantigen-specific T cells in a patient, we employ T cells of healthy donors with an overlapping HLA repertoire to target cancer neoantigens...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29525545/time-between-anterior-cruciate-ligament-injury-and-reconstruction-and-cartilage-metabolism-six-months-following-reconstruction
#12
Hope C Davis, Jeffery T Spang, Richard F Loeser, Staffan Larsson, Veronica Ulici, J Troy Blackburn, R Alexander Creighton, Ganesh M Kamath, Joanne M Jordan, Stephen W Marshall, Brian Pietrosimone
BACKGROUND: To determine the association between time from injury to ACL reconstruction (TimeInjury-ACLR ) and biochemical markers of cartilage metabolism and inflammation six months following ACL reconstruction (ACLR). METHODS: Individuals with a unilateral ACL injury were enrolled at initial presentation in the orthopedic clinic; blood was collected six months following ACLR. Enzyme-linked immunosorbent assays were used to analyze the ratio of serum concentrations of type-II collagen breakdown (C2C) to synthesis (CPII), plasma matrix metalloproteinase-3 (MMP-3), interleukin-6 (IL-6), and serum aggrecan neoepitope (ARGS)...
March 2018: Knee
https://www.readbyqxmd.com/read/29507106/the-immunogenicity-of-a-proline-substituted-altered-peptide-ligand-toward-the-cancer-associated-teipp-neoepitope-trh4-is-unrelated-to-complex-stability
#13
Ida Hafstrand, Elien M Doorduijn, Renhua Sun, Anna Talyzina, Marjolein Sluijter, Sara Pellegrino, Tatyana Sandalova, Adil Doganay Duru, Thorbald van Hall, Adnane Achour
Human cancers frequently display defects in Ag processing and presentation allowing for immune evasion, and they therefore constitute a significant challenge for T cell-based immunotherapy. We have previously demonstrated that the antigenicity of tumor-associated Ags can be significantly enhanced through unconventional residue modifications as a novel tool for MHC class I (MHC-I)-based immunotherapy approaches. We have also previously identified a novel category of cancer neo-epitopes, that is, T cell epitopes associated with impaired peptide processing (TEIPP), that are selectively presented by MHC-I on cells lacking the peptide transporter TAP...
April 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29505699/translating-immunopeptidomics-to-immunotherapy-decision-making-for-patient-and-personalized-target-selection
#14
Jens Fritsche, Barbara Rakitsch, Franziska Hoffgaard, Michael Römer, Heiko Schuster, Daniel J Kowalewski, Martin Priemer, Vlatka Stos-Zweifel, Helen Hörzer, Arun Satelli, Annika Sonntag, Valentina Goldfinger, Colette Song, Andrea Mahr, Martina Ott, Oliver Schoor, Toni Weinschenk
Immunotherapy is revolutionizing cancer treatment and has shown success in particular for tumors with a high mutational load. These effects have been linked to neoantigens derived from patient-specific mutations. To expand efficacious immunotherapy approaches to the vast majority of tumor types and patient populations carrying only a few mutations and maybe not a single presented neoepitope, it is necessary to expand the target space to non-mutated cancer-associated antigens. Mass spectrometry enables the direct and unbiased discovery and selection of tumor-specific human leukocyte antigen (HLA) peptides that can be used to define targets for immunotherapy...
March 5, 2018: Proteomics
https://www.readbyqxmd.com/read/29485848/subcutaneous-nanodisc-vaccination-with-neoantigens-for-combination-cancer-immunotherapy
#15
Rui Kuai, Xiaoqi Sun, Wenmin Yuan, Yao Xu, Anna Schwendeman, James J Moon
While cancer immunotherapy provides new exciting treatment options for patients, there is an urgent need for new strategies that can synergize with immune checkpoint blockers and boost the patient response rates. We have developed a personalized vaccine nanodisc platform based on synthetic high-density lipoproteins for co-delivery of immunostimulatory agents and tumor antigens, including tumor-specific neoantigens. Here we examined the route of delivery, safety profiles, and therapeutic efficacy of nanodisc vaccination against established tumors...
March 21, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29441070/a-recurrent-mutation-in-anaplastic-lymphoma-kinase-with-distinct-neoepitope-conformations
#16
Jugmohit S Toor, Arjun A Rao, Andrew C McShan, Mark Yarmarkovich, Santrupti Nerli, Karissa Yamaguchi, Ada A Madejska, Son Nguyen, Sarvind Tripathi, John M Maris, Sofie R Salama, David Haussler, Nikolaos G Sgourakis
The identification of recurrent human leukocyte antigen (HLA) neoepitopes driving T cell responses against tumors poses a significant bottleneck in the development of approaches for precision cancer therapeutics. Here, we employ a bioinformatics method, Prediction of T Cell Epitopes for Cancer Therapy, to analyze sequencing data from neuroblastoma patients and identify a recurrent anaplastic lymphoma kinase mutation ( ALK R1275Q) that leads to two high affinity neoepitopes when expressed in complex with common HLA alleles...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29409764/unsaturated-aldehyde-4-hydroxynonenal-hne-alters-the-structural-integrity-of-hsa-with-consequences-in-the-immuno-pathology-of-rheumatoid-arthritis
#17
Farzana Khan, Moinuddin, Abdul Rouf Mir, Sidra Islam, Minhal Abidi, Mohammed Amir Husain, Rizwan Hasan Khan
Human serum albumin (HSA) - the most abundant plasma protein plays an important role in the transport of endogenous and exogenous molecules in the body. Its modifications have been implicated in a variety of pathological disorders. We have studied the interaction of HNE with HSA at a molecular level by docking experiment and the results suggest a strong interaction between HNE and HSA. Immunological studies revealed that the circulating auto-antibodies in rheumatoid arthritis (RA) patients have a stronger affinity towards HNE-modified HSA...
June 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29409514/immune-monitoring-and-tcr-sequencing-of-cd4-t-cells-in-a-long-term-responsive-patient-with-metastasized-pancreatic-ductal-carcinoma-treated-with-individualized-neoepitope-derived-multipeptide-vaccines-a-case-report
#18
Katja Sonntag, Hisayoshi Hashimoto, Matthias Eyrich, Moritz Menzel, Max Schubach, Dennis Döcker, Florian Battke, Carolina Courage, Helmut Lambertz, Rupert Handgretinger, Saskia Biskup, Karin Schilbach
BACKGROUND: Cancer vaccines can effectively establish clinically relevant tumor immunity. Novel sequencing approaches rapidly identify the mutational fingerprint of tumors, thus allowing to generate personalized tumor vaccines within a few weeks from diagnosis. Here, we report the case of a 62-year-old patient receiving a four-peptide-vaccine targeting the two sole mutations of his pancreatic tumor, identified via exome sequencing. METHODS: Vaccination started during chemotherapy in second complete remission and continued monthly thereafter...
February 6, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29406501/recent-patents-in-neoantigens-and-neoepitopes
#19
(no author information available yet)
No abstract text is available yet for this article.
February 6, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29406493/putting-a-number-on-neoepitope-quality
#20
Irene Jarchum
No abstract text is available yet for this article.
February 6, 2018: Nature Biotechnology
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