Read by QxMD icon Read


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
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 7, 2018: Knee
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...
March 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Jens Fritsche, Barbara Rakitsch, Franziska Hoffgaard, Michael Römer, Heiko Schuster, Daniel J Kowalewski, Martin Priemer, Vlatka Stos-Zweifel, Helen Hoerzer, 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 neo-antigens 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 HLA peptides that can be used to define targets for immunotherapy...
March 5, 2018: Proteomics
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...
February 27, 2018: Bioconjugate Chemistry
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
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...
January 31, 2018: International Journal of Biological Macromolecules
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
(no author information available yet)
No abstract text is available yet for this article.
February 6, 2018: Nature Biotechnology
Irene Jarchum
No abstract text is available yet for this article.
February 6, 2018: Nature Biotechnology
Grammatiki Fotaki, Chuan Jin, Iliana Kyriaki Kerzeli, Mohanraj Ramachandran, Minttu-Maria Martikainen, Alex Karlsson-Parra, Di Yu, Magnus Essand
Autologous patient-derived dendritic cells (DCs) modified ex vivo to present tumor-associated antigens (TAAs) are frequently used as cancer vaccines. However, apart from the stringent logistics in producing DCs on a patient basis, accumulating evidence indicate that ex vivo engineered DCs are poor in migration and in fact do not directly present TAA epitopes to naïve T cells in vivo . Instead, it is proposed that bystander host DCs take up material from vaccine-DCs, migrate and subsequently initiate antitumor T-cell responses...
2018: Oncoimmunology
R Palankar, T P Kohler, K Krauel, J Wesche, S Hammerschmidt, A Greinacher
BACKGROUND: Activated platelets release the chemokine platelet factor 4 (PF4) stored in their granules. PF4 binds to polyanions (P) on bacteria, undergoes a conformational change and exposes neoepitopes. These neoepitopes induce production of anti-PF4/P antibodies. As PF4 binds to a variety of bacteria, anti-PF4/P IgG can bind and opsonize several bacterial species. OBJECTIVE: Here we investigated whether platelets are able to kill bacteria directly after recognizing anti-PF4/P IgG opsonized bacteria in the presence of PF4 via their FcγRIIA...
January 19, 2018: Journal of Thrombosis and Haemostasis: JTH
Kristen K Ciombor, Richard M Goldberg
Microsatellite instability-high/DNA mismatch repair deficient tumors are found across the cancer spectrum and often harbor markedly increased numbers of mutations when compared to microsatellite stable/DNA mismatch repair proficient tumors. As a result of this high mutational load, tumor-infiltrating lymphocyte density is increased and more immunogenic neoepitopes are expressed, leading to upregulation of immune checkpoints in these tumors. Checkpoint inhibitors such as pembrolizumab and nivolumab, both immunoglobulin G4 (IgG4) monoclonal antibodies that block interactions between the programmed cell death receptor-1 and its ligands, have significant activity in this tumor class...
January 19, 2018: Drugs
Zhuting Hu, Patrick A Ott, Catherine J Wu
Cancer vaccines, which are designed to amplify tumour-specific T cell responses through active immunization, have long been envisioned as a key tool of effective cancer immunotherapy. Despite a clear rationale for such vaccines, extensive past efforts were unsuccessful in mediating clinically relevant antitumour activity in humans. Recently, however, next-generation sequencing and novel bioinformatics tools have enabled the systematic discovery of tumour neoantigens, which are highly desirable immunogens because they arise from somatic mutations of the tumour and are therefore tumour specific...
March 2018: Nature Reviews. Immunology
Myriam Martin, Karolina I Smoląg, Albin Björk, Birgitta Gullstrand, Marcin Okrój, Jonatan Leffler, Andreas Jönsen, Anders A Bengtsson, Anna M Blom
BACKGROUND: In the present study, we sought to evaluate the complement activation product C4d as a marker for lupus nephritis in systemic lupus erythematosus (SLE). METHODS: C4d levels were determined by enzyme-linked immunosorbent assay in plasma samples of patients with established SLE using a novel approach based on detection of a short linear cleavage neoepitope. Cross-sectional associations were studied in 98 patients with SLE with samples taken at lower or higher respective disease activity...
December 6, 2017: Arthritis Research & Therapy
Yasumori Sobue, Toshihisa Kojima, Kazutoshi Kurokouchi, Shigeo Takahashi, Hiroaki Yoshida, Robin Poole, Naoki Ishiguro
BACKGROUND: We aimed to determine whether synovial fluid (SF) biomarkers can predict the progression of articular cartilage damage as determined by arthroscopic evaluation during and after anterior cruciate ligament (ACL) reconstruction. METHODS: Arthroscopic assessment of articular cartilage damage was performed twice in 62 patients, first during ACL reconstruction and then approximately 2 years later during implant removal for ligament fixation. SF levels of the collagenase-generated cleavage neoepitope of type II collagen (C2C) and proteoglycan glycosaminoglycans keratan sulfate (KS), chondroitin-4-sulfate (Δdi-C4S), and chondroitin-6-sulfate (Δdi-C6S) were measured at ACL reconstruction...
December 6, 2017: Arthritis Research & Therapy
Zinal S Chheda, Gary Kohanbash, Kaori Okada, Naznin Jahan, John Sidney, Matteo Pecoraro, Xinbo Yang, Diego A Carrera, Kira M Downey, Shruti Shrivastav, Shuming Liu, Yi Lin, Chetana Lagisetti, Pavlina Chuntova, Payal B Watchmaker, Sabine Mueller, Ian F Pollack, Raja Rajalingam, Angel M Carcaboso, Matthias Mann, Alessandro Sette, K Christopher Garcia, Yafei Hou, Hideho Okada
The median overall survival for children with diffuse intrinsic pontine glioma (DIPG) is less than one year. The majority of diffuse midline gliomas, including more than 70% of DIPGs, harbor an amino acid substitution from lysine (K) to methionine (M) at position 27 of histone 3 variant 3 (H3.3). From a CD8+ T cell clone established by stimulation of HLA-A2+ CD8+ T cells with synthetic peptide encompassing the H3.3K27M mutation, complementary DNA for T cell receptor (TCR) α- and β-chains were cloned into a retroviral vector...
January 2, 2018: Journal of Experimental Medicine
Diana J Leeming, Inger Byrjalsen, Jannie M B Sand, Asger R Bihlet, Peter Lange, Ruth Thal-Singer, Bruce E Miller, Morten A Karsdal, Jørgen Vestbo
BACKGROUND: Change in forced expiratory volume in one second (FEV1 ) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1 . METHODS: One thousand COPD subjects from the observational, multicentre, three-year ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study (NCT00292552, trial registration in February 2006) were included...
December 4, 2017: BMC Pulmonary Medicine
Anne-Mette Bjerregaard, Morten Nielsen, Vanessa Jurtz, Carolina M Barra, Sine Reker Hadrup, Zoltan Szallasi, Aron Charles Eklund
Personalization of cancer immunotherapies such as therapeutic vaccines and adoptive T-cell therapy may benefit from efficient identification and targeting of patient-specific neoepitopes. However, current neoepitope prediction methods based on sequencing and predictions of epitope processing and presentation result in a low rate of validation, suggesting that the determinants of peptide immunogenicity are not well understood. We gathered published data on human neopeptides originating from single amino acid substitutions for which T cell reactivity had been experimentally tested, including both immunogenic and non-immunogenic neopeptides...
2017: Frontiers in Immunology
Jennifer Brooks, Bettina Fleischmann-Mundt, Norman Woller, Julia Niemann, Silvia Ribback, Kristin Peters, Ihsan Ekin Demir, Nina Armbrecht, Guralp O Ceyhan, Michael P Manns, Thomas C Wirth, Stefan Kubicka, Gunter Bernhardt, Mark J Smyth, Diego F Calvisi, Engin Gürlevik, Florian Kühnel
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and disseminating cancer resistant to therapy, including checkpoint immunotherapies, and early tumor resection and (neo)adjuvant chemotherapy fails to improve a poor prognosis. In a transgenic mouse model of resectable PDAC, we investigated the coordinated activation of T and natural killier (NK) cells in addition to gemcitabine chemotherapy to prevent tumor recurrence. Only neoadjuvant, but not adjuvant treatment with a PD-1 antagonist effectively supported chemotherapy and suppressed local tumor recurrence and improved survival involving both NK and T cells...
January 15, 2018: Cancer Research
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"