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https://www.readbyqxmd.com/read/28228279/loss-of-pten-is-associated-with-resistance-to-anti-pd-1-checkpoint-blockade-therapy-in-metastatic-uterine-leiomyosarcoma
#1
Suzanne George, Diana Miao, George D Demetri, Dennis Adeegbe, Scott J Rodig, Sachet Shukla, Mikel Lipschitz, Ali Amin-Mansour, Chandrajit P Raut, Scott L Carter, Peter Hammerman, Gordon J Freeman, Catherine J Wu, Patrick A Ott, Kwok-Kin Wong, Eliezer M Van Allen
Response to immune checkpoint blockade in mesenchymal tumors is poorly characterized, but immunogenomic dissection of these cancers could inform immunotherapy mediators. We identified a treatment-naive patient who has metastatic uterine leiomyosarcoma and has experienced complete tumor remission for >2 years on anti-PD-1 (pembrolizumab) monotherapy. We analyzed the primary tumor, the sole treatment-resistant metastasis, and germline tissue to explore mechanisms of immunotherapy sensitivity and resistance...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28217703/babesiosis-associated-immune-thrombocytopenia
#2
Roshni Narurkar, Aleksandra Mamorska-Dyga, Anup Agarwal, John C Nelson, Delong Liu
Thrombocytopenia is a common feature of babesiosis. The mechanism for thrombocytopenia in babesiosis remains elusive. We report a case of babesiosis with severe new onset immune thrombocytopenia (ITP). In addition to antibiotics treatment for babesiosis, ITP therapy was administered. ITP in the present case was most likely triggered by the babesia infection. The severity of ITP in this case was not proportional to the severity of parasitemia. The neoantigen triggering the autoimmune response in babesiosis requires further characterization...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28210865/the-impact-of-melanoma-genetics-on-treatment-response-and-resistance-in-clinical-and-experimental-studies
#3
M Kunz, M Hölzel
Recent attempts to characterize the melanoma mutational landscape using high-throughput sequencing technologies have identified new genes and pathways involved in the molecular pathogenesis of melanoma. Apart from mutated BRAF, NRAS, and KIT, a series of new recurrently mutated candidate genes with impact on signaling pathways have been identified such as NF1, PTEN, IDH1, RAC1, ARID2, and TP53. Under targeted treatment using BRAF and MEK1/2 inhibitors either alone or in combination, a majority of patients experience recurrences, which are due to different genetic mechanisms such as gene amplifications of BRAF or NRAS, MEK1/2 and PI3K mutations...
February 16, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28202532/cd40-signaling-drives-potent-cellular-immune-responses-in-heterologous-cancer-vaccinations
#4
Supot Nimanong, Dmitrij Ostroumov, Jessica Wingerath, Sarah Knocke, Norman Woller, Engin Guerlevik, Christine Falk, Michael P Manns, Florian Kuehnel, Thomas C Wirth
Antagonistic antibodies targeting co-inhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited due to insufficient induction of adaptive immune responses. Here we describe a novel vaccination method consisting of a primary dendritic cell immunization followed by a composite vaccination including an agonistic CD40 antibody, soluble antigen and a TLR3 agonist, referred to as CoAT...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28198830/-final-common-pathway-of-human-cancer-immunotherapy-targeting-random-somatic-mutations
#5
REVIEW
Eric Tran, Paul F Robbins, Steven A Rosenberg
Effective clinical cancer immunotherapies, such as administration of the cytokine IL-2, adoptive cell transfer (ACT) and the recent success of blockade of the checkpoint modulators CTLA-4 and PD-1, have been developed without clear identification of the immunogenic targets expressed by human cancers in vivo. Immunotherapy of patients with cancer through the use of ACT with autologous lymphocytes has provided an opportunity to directly investigate the antigen recognition of lymphocytes that mediate cancer regression in humans...
February 15, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28187283/applications-of-immunogenomics-to-cancer
#6
REVIEW
X Shirley Liu, Elaine R Mardis
Cancer immunogenomics originally was framed by research supporting the hypothesis that cancer mutations generated novel peptides seen as "non-self" by the immune system. The search for these "neoantigens" has been facilitated by the combination of new sequencing technologies, specialized computational analyses, and HLA binding predictions that evaluate somatic alterations in a cancer genome and interpret their ability to produce an immune-stimulatory peptide. The resulting information can characterize a tumor's neoantigen load, its cadre of infiltrating immune cell types, the T or B cell receptor repertoire, and direct the design of a personalized therapeutic...
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28178261/the-problem-with-neoantigen-prediction
#7
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
February 8, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28175395/143%C3%A2-identification-of-neoantigen-specific-cd8-t-cells-in-two-murine-orthotopic-glioblastoma-models-using-cancer-immunogenomics
#8
Tanner M Johanns, Jeffrey Ward, Courtney Wilson, Dale K Kobayashi, Diane Bender, Yujie Fu, Anton Alexandrov, Maxim N Artyomov, Chris A Miller, Elaine R Mardis, Gavin P Dunn
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
https://www.readbyqxmd.com/read/28169993/the-evolving-genomic-landscape-of-urothelial-carcinoma
#9
REVIEW
Alexander P Glaser, Damiano Fantini, Ali Shilatifard, Edward M Schaeffer, Joshua J Meeks
Survival of patients with urothelial carcinoma (including bladder cancer and upper tract urothelial carcinoma) is limited by our current approaches to staging, surgery, and chemotherapy. Large-scale, next-generation sequencing collaborations, such as The Cancer Genome Atlas, have already identified drivers and vulnerabilities of urothelial carcinoma. This disease has a high degree of mutational heterogeneity and a high frequency of somatic mutations compared with other solid tumours, potentially resulting in an increased neoantigen burden...
February 7, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28116322/genetically-modified-t-cell-based-adoptive-immunotherapy-in-hematological-malignancies
#10
REVIEW
Baixin Ye, Creed M Stary, Qingping Gao, Qiongyu Wang, Zhi Zeng, Zhihong Jian, Lijuan Gu, Xiaoxing Xiong
A significant proportion of hematological malignancies remain limited in treatment options. Immune system modulation serves as a promising therapeutic approach to eliminate malignant cells. Cytotoxic T lymphocytes (CTLs) play a central role in antitumor immunity; unfortunately, nonspecific approaches for targeted recognition of tumor cells by CTLs to mediate tumor immune evasion in hematological malignancies imply multiple mechanisms, which may or may not be clinically relevant. Recently, genetically modified T-cell-based adoptive immunotherapy approaches, including chimeric antigen receptor (CAR) T-cell therapy and engineered T-cell receptor (TCR) T-cell therapy, promise to overcome immune evasion by redirecting the specificity of CTLs to tumor cells...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28116089/it-s-a-long-way-to-the-top-if-you-want-to-personalize-immunotherapy
#11
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/28114254/adoptive-cell-therapy-for-metastatic-melanoma
#12
Efrat Merhavi-Shoham, Orit Itzhaki, Gal Markel, Jacob Schachter, Michal J Besser
Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TILs) is a powerful form of immunotherapy by inducing durable complete responses that significantly extend the survival of melanoma patients. Mutation-derived neoantigens were recently identified as key factors for tumor recognition and rejection by TILs. The isolation of T-cell receptor (TCR) genes directed against neoantigens and their retransduction into peripheral T cells may provide a new form of ACT.Genetic modifications of T cells with chimeric antigen receptors (CARs) have demonstrated remarkable clinical results in hematologic malignancies, but are so far less effective in solid tumors...
January 2017: Cancer Journal
https://www.readbyqxmd.com/read/28111041/-tissue-biomarkers-of-response-to-anti-pd-1-immunotherapies-in-melanoma
#13
Julien Adam, Gorana Tomasic, Caroline Robert
Prognosis and treatment of advanced melanoma have been transformed by the success of immunotherapies, in particular agents targeting PD-1. PD-L1 expression assessed by immunohistochemistry in not an effective predictive biomarker to select patients in this tumor type, since significant clinical benefit was observed in the group of patients with negative tumors. The predictive value of PD-L1 testing to select patients for combination of anti-PD-1 and anti-CTLA-4 agents is under evaluation. Other tissue biomarkers are emerging to identify sensitive tumors to anti-PD-1 agents...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28109401/melanoma-last-call-for-radiotherapy
#14
REVIEW
Sophie Espenel, Alexis Vallard, Chloé Rancoule, Max-Adrien Garcia, Jean-Baptiste Guy, Cyrus Chargari, Eric Deutsch, Nicolas Magné
Melanoma is traditionally considered to be a radioresistant tumor. However, radiotherapy and immunotherapy latest developments might upset this radiobiological dogma. Stereotactic radiotherapy allows high dose per fraction delivery, with high dose rate. More DNA lethal damages, less sublethal damages reparation, endothelial cell apoptosis, and finally clonogenic cell dysfunction are produced, resulting in improved local control. Radiotherapy can also enhance immune responses, inducing neoantigens formation, tumor antigen presentation, and cytokines release...
February 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28104820/immune-checkpoint-inhibitors-in-malignancies-with-mismatch-repair-deficiency-a-review-of-the-state-of-the-current-knowledge
#15
Ali Naboush, Christopher A J Roman, Iuliana Shapira
The use of immune checkpoint inhibitors to treat malignant tumors with microsatellite instability is an emerging new modality. This is based on the observations that these tumors may have a high mutation rate-thus a potential source of tumor-specific neoantigens-and harbor infiltrating cytotoxic T cells in response, suggesting that they may be particularly susceptible to immune checkpoint therapy. PUBMED and ASCO library were systematically reviewed to identify all relevant data that involved the use of immune checkpoint inhibitors in the treatment of cancers with microsatellite instability...
January 19, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28104443/mhc-class-ii-restricted-neoantigen-a-promising-target-in-tumor-immunotherapy
#16
Zhichen Sun, Fangjun Chen, Fanyan Meng, Jia Wei, Baorui Liu
Neoantigen is a patient-specific tumor antigen resulted from mutations during oncogenesis. Emerging data suggested that immune responsiveness against neoantigens correlated with the success of clinical tumor immunotherapies. Nowadays, the majority of studies on neoantigens have focused on MHC class I restricted antigens recognized by CD8+ T cells. With improved understanding of the underlying principles of tumor biology and immunology, increasing emphasis has been put on CD4+ T cells and MHC class II restricted antigens...
January 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28093357/are-the-innate-and-adaptive-immune-systems-setting-hypertension-on-fire
#17
REVIEW
Gisele F Bomfim, Fernanda Luciano Rodrigues, Fernando S Carneiro
Hypertension is the most common chronic cardiovascular disease and is associated with several pathological states, being an important cause of morbidity and mortality around the world. Low-grade inflammation plays a key role in hypertension and the innate and adaptive immune systems seem to contribute to hypertension development and maintenance. Hypertension is associated with vascular inflammation, increased vascular cytokines levels and infiltration of immune cells in the vasculature, kidneys and heart. However, the mechanisms that trigger inflammation and immune system activation in hypertension are completely unknown...
January 16, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28088513/an-immunogram-for-the-cancer-immunity-cycle-towards-personalized-immunotherapy-of-lung-cancer
#18
Takahiro Karasaki, Kazuhiro Nagayama, Hideki Kuwano, Jun-Ichi Nitadori, Masaaki Sato, Masaki Anraku, Akihiro Hosoi, Hirokazu Matsushita, Yasuyuki Morishita, Kosuke Kashiwabara, Masaki Takazawa, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
INTRODUCTION: The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of antitumor immunity as a dynamic spatiotemporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle by using next-generation sequencing. METHODS: Whole exome sequencing and RNA sequencing were performed in 20 patients with NSCLC (12 with adenocarcinoma, seven with squamous cell carcinoma, and one with large cell neuroendocrine carcinoma)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28077675/post-hoc-assessment-of-the-immunogenicity-of-bioengineered-factor-viia-demonstrates-the-use-of-preclinical-tools
#19
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/28074226/synergistic-effects-of-host-b7-h4-deficiency-and-gemcitabine-treatment-on-tumor-regression-and-anti-tumor-t-cell-immunity-in-a-mouse-model
#20
Joanne Leung, Philippe St-Onge, John Stagg, Woong-Kyung Suh
B7-H4 (B7x/B7S1), a B7 family inhibitor of T cell activity, is expressed in multiple human cancers and correlates with decreased infiltrating lymphocytes and poor prognosis. In murine models, tumor-expressed B7-H4 enhances tumor growth and reduces T cell immunity, and blockade of tumor-B7-H4 rescues T cell activity and lowers tumor burden. This implicates B7-H4 as a target for cancer immunotherapy, yet limits the efficacy of B7-H4 blockade exclusively to patients with B7-H4+ tumors. Given the expression of B7-H4 on host immune cells, we have previously shown that BALB/c mice lacking host B7-H4 have enhanced anti-tumor profiles, yet similar 4T1 tumor growth relative to control...
January 10, 2017: Cancer Immunology, Immunotherapy: CII
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