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Neoepitopes

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https://www.readbyqxmd.com/read/28533942/hla-a24-ligandome-analysis-of-colon-and-lung-cancer-cells-identifies-a-novel-cancer-testis-antigen-and-a-neoantigen-that-elicits-specific-and-strong-ctl-responses
#1
Vitaly Kochin, Takayuki Kanaseki, Serina Tokita, Sho Miyamoto, Yosuke Shionoya, Yasuhiro Kikuchi, Daichi Morooka, Yoshihiko Hirohashi, Tomohide Tsukahara, Kazue Watanabe, Shingo Toji, Yasuo Kokai, Noriyuki Sato, Toshihiko Torigoe
This study focused on HLA-A24 and comprehensively analyzed the ligandome of colon and lung cancer cells without the use of MHC-binding in silico prediction algorithms. Affinity purification using the antibody specific to HLA-A24 followed by LC-MS/MS sequencing was used to detect peptides, which harbored the known characteristics of HLA-A24 peptides in terms of length and anchor motifs. Ligandome analysis demonstrated the natural presentation of two different types of novel tumor-associated antigens. The ligandome contained a peptide derived from SUV39H2, a gene found to be expressed in a variety of cancers but not in normal tissues (except for the testis)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28526919/antibodies-to-post-translationally-modified-insulin-as-a-novel-biomarker-for-prediction-of-type-1-diabetes-in-children
#2
Rocky Strollo, Chiara Vinci, Nicola Napoli, Paolo Pozzilli, Johnny Ludvigsson, Ahuva Nissim
AIMS/HYPOTHESIS: We have shown that autoimmunity to insulin in type 1 diabetes may result from neoepitopes induced by oxidative post-translational modifications (oxPTM). Antibodies specific to oxPTM-insulin (oxPTM-INS-Ab) are present in most newly diagnosed individuals with type 1 diabetes and are more common than autoantibodies to native insulin. In this study, we investigated whether oxPTM-INS-Ab are present before clinical onset of type 1 diabetes, and evaluated the ability of oxPTM-INS-Ab to identify children progressing to type 1 diabetes...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28511649/il-10-ameliorates-tnf-%C3%AE-induced-meniscus-degeneration-in-mature-meniscal-tissue-in-vitro
#3
P Behrendt, K Häfelein, A Preusse-Prange, A Bayer, A Seekamp, B Kurz
BACKGROUND: Joint inflammation causes meniscus degeneration and can exacerbate post-traumatic meniscus injuries by extracellular matrix degradation, cellular de-differentiation and cell death. The aim of this study was to examine whether anti-inflammatory interleukin-10 exerts protective effects in an in vitro model of TNF-α-induced meniscus degeneration. METHODS: Meniscus tissue was harvested from the knees of adult cows. After 24 h of equilibrium explants were simultaneously treated with bovine TNF-α and IL-10...
May 16, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28473443/relationship-of-autoantibodies-to-mda-ldl-and-apob-immune-complexes-to-sex-ethnicity-subclinical-atherosclerosis-and-cardiovascular-events
#4
Anand Prasad, Paul Clopton, Colby Ayers, Amit Khera, James A de Lemos, Joseph L Witztum, Sotirios Tsimikas
OBJECTIVE: Modifications of lipid constituents within atherosclerotic lesions generate neoepitopes that activate innate and adaptive immune responses. We aimed to define the prevalence, distribution, and relationship of autoantibody titers of oxidized lipoproteins to subclinical atherosclerosis and major adverse cardiovascular events (MACE) in different ethnic groups. APPROACH AND RESULTS: IgG and IgM autoantibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and apolipoprotein B-100-immune complexes were measured in 3509 individuals (1814 blacks, 1031 whites, 589 Hispanics, and 85 no race identifier) from the Dallas Heart Study with median 10...
May 4, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28473207/quantification-of-cartilage-oligomeric-matrix-protein-comp-and-a-comp-neoepitope-in-synovial-fluid-of-patients-with-different-joint-disorders-by-novel-automated-assays
#5
P Lorenzo, A Aspberg, T Saxne, P Önnerfjord
OBJECTIVE: To develop automated immunoassays for the quantification of Cartilage Oligomeric Matrix Protein (COMP) and a COMP neoepitope in synovial fluid and to investigate their diagnostic potential in different joint conditions. METHODS: Two sandwich immunoassays were developed for the quantification of COMP and a COMP neoepitope, using an automated analyser (IDS-iSYS, Immunodiagnostic Systems, Boldon, UK). Assay performance was evaluated in terms of sensitivity, recovery, linearity, and intra- and inter-assay precision...
May 2, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28431875/protein-oxidation-and-autoantibodies-reactivity-against-malondialdehyde-and-hydrogen-peroxide-modified-thyroid-antigens-in-plasma-of-patients-with-graves-disease-and-hashimoto-thyroiditis
#6
Malek Mseddi, Riadh Ben Mansour, Bochra Gargouri, Fatma Mnif, Samir El Ghawi, Boutheina Hammami, Abdelmonem Ghorbel, Mohamed Abid, Saloua Lassoued
The aim of this study was first to investigate the oxidative proteins modifications in the plasma of both autoimmune thyroid diseases (AITD), Graves' disease (GD) and Hashimoto Thyroiditis (HT). Then, the impact of these oxidative modifications on immune response was evaluated by measuring the reactivity of patients' autoantibodies against malondialdéhyde (MDA) and Hydrogen peroxide (H2O2) modified thyroid antigens (T.Ag) in comparison to native ones. Carbonyl and thiol groups, and MDA-protein adducts were first assessed among 74 AITD patients and 65 healthy controls...
April 18, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28380609/age-related-effects-on-markers-of-inflammation-and-cartilage-metabolism-in-response-to-an-intra-articular-lipopolysaccharide-challenge-in-horses
#7
M K Kahn, J A Coverdale, J L Leatherwood, C E Arnold, R A Dabareiner, A N Bradbery, A A Millican, T H Welsh
Eighteen Quarter Horses were used in a randomized complete design for a 28-d experiment to evaluate age-related effects on inflammation and cartilage turnover after induction of a single inflammatory insult using lipopolysaccharide (LPS). Horses were grouped by age as yearlings (3 males and 3 females), 2 to 3 yr olds (2/3 yr old; 2 males and 4 females), and skeletally mature 5 to 8 yr olds (mature; 2 males and 4 females). On d 0, all horses were individually housed and fed diets that met or exceeded requirements...
February 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28349070/diabetes-is-associated-with-increased-autoreactivity-of-mannan-binding-lectin
#8
Esben Axelgaard, Jakob Appel Østergaard, Steffen Thiel, Troels Krarup Hansen
Mannan-binding lectin (MBL) has been reported to be involved in the pathophysiology of diabetic nephropathy. MBL is a pattern-recognition molecule of the innate immune system that initiates the lectin pathway of the complement system upon recognition of evolutionary conserved pathogen-associated molecular patterns or to altered self-tissue. Our group have previously shown direct effects of MBL on diabetes-induced kidney damage, and we hypothesized that MBL may cause autoactivation of the complement system via binding to neoepitopes induced by hyperglycemia...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28303769/neoepitopes-as-cancer-immunotherapy-targets-key-challenges-and-opportunities
#9
Cory A Brennick, Mariam M George, William L Corwin, Pramod K Srivastava, Hakimeh Ebrahimi-Nik
Over the last half century, it has become well established that cancers can elicit a host immune response that can target them with high specificity. Only within the last decade, with the advances in high-throughput gene sequencing and bioinformatics approaches, are we now on the forefront of harnessing the host's immune system to treat cancer. Recently, some strides have been taken toward understanding effective tumor-specific MHC I restricted epitopes or neoepitopes. However, many fundamental questions still remain to be addressed before this therapy can live up to its full clinical potential...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28280852/tantigen-a-comprehensive-database-of-tumor-t-cell-antigens
#10
Lars Rønn Olsen, Songsak Tongchusak, Honghuang Lin, Ellis L Reinherz, Vladimir Brusic, Guang Lan Zhang
Tumor T cell antigens are both diagnostically and therapeutically valuable molecules. A large number of new peptides are examined as potential tumor epitopes each year, yet there is no infrastructure for storing and accessing the results of these experiments. We have retroactively cataloged more than 1000 tumor peptides from 368 different proteins, and implemented a web-accessible infrastructure for storing and accessing these experimental results. All peptides in TANTIGEN are labeled as one of the four categories: (1) peptides measured in vitro to bind the HLA, but not reported to elicit either in vivo or in vitro T cell response, (2) peptides found to bind the HLA and to elicit an in vitro T cell response, (3) peptides shown to elicit in vivo tumor rejection, and (4) peptides processed and naturally presented as defined by physical detection...
March 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28257957/the-cancer-immunity-cycle-as-rational-design-for-synthetic-cancer-drugs-novel-dc-vaccines-and-car-t-cells
#11
REVIEW
Mohanraj Ramachandran, Anna Dimberg, Magnus Essand
Cell therapy is an advanced form of cancer immunotherapy that has had remarkable clinical progress in the past decade in the search for cure of cancer. Most success has been achieved for chimeric antigen receptor (CAR) T-cells where CAR T-cells targeting CD19 show very high complete response rates for patients with refractory acute B-cell acute lymphoblastic leukemia (ALL) and are close to approval for this indication. CD19 CAR T-cells are also effective against B-cell chronic lymphoblastic leukemia (CLL) and B-cell lymphomas...
February 28, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28168551/differences-in-type-ii-collagen-turnover-of-osteoarthritic-human-knee-and-ankle-joints
#12
Matthias Aurich, Gunther O Hofmann, Bernd Rolauffs
PURPOSE: We analysed hyaline cartilage of human knee and ankle joints for collagen and proteoglycan turnover in order to find differences in the metabolism and biochemical content of the extracellular matrix that could explain the higher prevalence of osteoarthritis (OA) in the knee joint, compared to the ankle joint. METHODS: Cartilage tissue from ankle and knee joints of OA patients were assessed for total collagen and proteoglycan content. For turnover, the aggrecan 846-epitope (CS 846), the type II collagen C-propeptide (CP2) and the collagenase-generated intrahelical cleavage neoepitope (C2C) were quantified...
February 6, 2017: International Orthopaedics
https://www.readbyqxmd.com/read/28116089/it-s-a-long-way-to-the-top-if-you-want-to-personalize-immunotherapy
#13
EDITORIAL
Sarah Haebe, Oliver Weigert
Harnessing the immune system to attack tumor cells by targeting tumor-associated or -preferably- tumor-specific antigens has emerged as a promising but challenging treatment option for malignant lymphomas. Follicular lymphoma is among the most common lymphomas worldwide and remains incurable for most patients. Considered to be an immunogenic disease it represents an interesting disease entity for various immunotherapeutic approaches. In an article published in the May issue of Clinical Cancer Research, Nielsen and colleagues provided important proof-of-principle data on the immunogenicity of follicular lymphoma that might represent a first step towards personalized adoptive immunotherapies in this disease...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28100240/reactivation-of-dormant-anti-tumor-immunity-a-clinical-perspective-of-therapeutic-immune-checkpoint-modulation
#14
REVIEW
Richard Greil, Evelyn Hutterer, Tanja Nicole Hartmann, Lisa Pleyer
In favor of their outgrowth, cancer cells must resist immune surveillance and edit the immune response. Cancer immunoediting is characterized by fundamental changes in the cellular composition and the inflammatory cytokine profiles in the microenvironment of the primary tumor and metastatic niches, with an ever increasing complexity of interactions between tumor cells and the immune system. Recent data suggest that genetic instability and immunoediting are not necessarily disparate processes. Increasing mutational load may be associated with multiple neoepitopes expressed by the tumor cells and thus increased chances for the immune system to recognize and combat these cells...
January 19, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28077675/post-hoc-assessment-of-the-immunogenicity-of-bioengineered-factor-viia-demonstrates-the-use-of-preclinical-tools
#15
Kasper Lamberth, Stine Louise Reedtz-Runge, Jonathan Simon, Ksenia Klementyeva, Gouri Shankar Pandey, Søren Berg Padkjær, Véronique Pascal, Ileana R León, Charlotte Nini Gudme, Søren Buus, Zuben E Sauna
Immunogenicity is an important consideration in the licensure of a therapeutic protein because the development of neutralizing anti-drug antibodies (ADAs) can affect both safety and efficacy. Neoantigens introduced by bioengineering of a protein drug are a particular cause for concern. The development of a bioengineered recombinant factor VIIa (rFVIIa) analog was discontinued after phase 3 trials because of the development of ADAs. The unmodified parent molecule (rFVIIa), on the other hand, has been successfully used as a drug for more than two decades with no reports of immunogenicity in congenital hemophilia patients with inhibitors...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28007776/immune-cytolytic-activity-stratifies-molecular-subsets-of-human-pancreatic-cancer
#16
David Balli, Andrew J Rech, Ben Z Stanger, Robert H Vonderheide
PURPOSE: Immunotherapy has the potential to improve the dismal prognosis in pancreatic ductal adenocarcinoma (PDA), but clinical trials - including those with single-agent PD-1/PD-L1 inhibition - have been disappointing. Our aim was to examine the immune landscape of PDA as it relates to aspects of tumor biology, including neoepitope burden. EXPERIMENTAL DESIGN: We used publically available expression data from 134 primary resection PDA samples from The Cancer Genome Atlas to stratify patients according to a cytolytic T-cell activity expression index...
December 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27956380/somatic-mutations-and-neoepitope-homology-in-melanomas-treated-with-ctla-4-blockade
#17
Tavi Nathanson, Arun Ahuja, Alexander Rubinsteyn, Bulent Arman Aksoy, Matthew D Hellmann, Diana Miao, Eliezer Van Allen, Taha Merghoub, Jedd D Wolchok, Alexandra Snyder, Jeff Hammerbacher
Immune checkpoint inhibitors are promising treatments for patients with a variety of malignancies. Toward understanding the determinants of response to immune checkpoint inhibitors, it was previously demonstrated that the presence of somatic mutations is associated with benefit from checkpoint inhibition. A hypothesis was posited that neoantigen homology to pathogens may in part explain the link between somatic mutations and response. To further examine this hypothesis, we reanalyzed cancer exome data obtained from our previously published study of 64 melanoma patients treated with CTLA-4 blockade and a new dataset of RNA-Seq data from 24 of these patients...
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/27931265/increased-caspase-6-activity-in-the-human-anterior-olfactory-nuclei-of-the-olfactory-bulb-is-associated-with-cognitive-impairment
#18
Benedicte Foveau, Steffen Albrecht, David A Bennett, José A Correa, Andrea C LeBlanc
Abnormally elevated hippocampal Caspase-6 (Casp6) activity is intimately associated with age-related cognitive impairment in humans and in mice. In humans, these high levels of Casp6 activity are initially localized in the entorhinal cortex, the area of the brain first affected by the formation of neurofibrillary tangles, according to Braak staging. The reason for the high vulnerability of entorhinal cortex neurons to neurofibrillary tangle pathology and Casp6 activity is unknown. Casp6 activity is involved in axonal degeneration, therefore, one possibility to explain increased vulnerability of the entorhinal cortex neurons would be that the afferent neurons of the olfactory bulb, some of which project their axons to the entorhinal cortex, are equally degenerating...
December 8, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27869121/direct-identification-of-clinically-relevant-neoepitopes-presented-on-native-human-melanoma-tissue-by-mass-spectrometry
#19
Michal Bassani-Sternberg, Eva Bräunlein, Richard Klar, Thomas Engleitner, Pavel Sinitcyn, Stefan Audehm, Melanie Straub, Julia Weber, Julia Slotta-Huspenina, Katja Specht, Marc E Martignoni, Angelika Werner, Rüdiger Hein, Dirk H Busch, Christian Peschel, Roland Rad, Jürgen Cox, Matthias Mann, Angela M Krackhardt
Although mutations may represent attractive targets for immunotherapy, direct identification of mutated peptide ligands isolated from human leucocyte antigens (HLA) on the surface of native tumour tissue has so far not been successful. Using advanced mass spectrometry (MS) analysis, we survey the melanoma-associated immunopeptidome to a depth of 95,500 patient-presented peptides. We thereby discover a large spectrum of attractive target antigen candidates including cancer testis antigens and phosphopeptides...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27864551/immunological-outcomes-of-antibody-binding-to-glycans-shared-between-microorganisms-and-mammals
#20
REVIEW
Preeyam Patel, John F Kearney
Glycans constitute basic cellular components of living organisms across biological kingdoms, and glycan-binding Abs participate in many cellular interactions during immune defense against pathogenic organisms. Glycan epitopes are expressed as carbohydrate-only entities or as oligomers or polymers on proteins and lipids. Such epitopes on glycoproteins may be formed by posttranslational modifications or neoepitopes resulting from metabolic-catabolic processes and can be altered during inflammation. Pathogenic organisms can display host-like glycans to evade the host immune response...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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