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Immunotherapy

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https://www.readbyqxmd.com/read/29352713/clinical-variables-associated-with-overall-survival-in-metastatic-castration-resistant-prostate-cancer-patients-treated-with-sipuleucel-t-immunotherapy
#1
Xiao X Wei, Jaselle Perry, Emily Chang, Li Zhang, Robert A Hiatt, Charles J Ryan, Eric J Small, Lawrence Fong
BACKGROUND: Sipuleucel-T is an autologous cell-based cancer immunotherapy for men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its approval by the Food and Drug Administration was based on demonstration of an overall survival (OS) benefit in randomized placebo-controlled phase III trials. However, treatment was associated with a prostate-specific antigen (PSA) decline in only a small minority of patients. Understanding the clinical factors that are associated with OS could help guide treatment decisions, including patient selection and the timing of sipuleucel-T relative to other therapies...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29352387/current-perspectives-on-erythema-multiforme
#2
REVIEW
Marianne Lerch, Carlo Mainetti, Benedetta Terziroli Beretta-Piccoli, Thomas Harr
Recognition and timely adequate treatment of erythema multiforme remain a major challenge. In this review, current diagnostic guidelines, potential pitfalls, and modern/novel treatment options are summarized with the aim to help clinicians with diagnostic and therapeutic decision-making. The diagnosis of erythema multiforme, that has an acute, self-limiting course, is based on its typical clinical picture of targetoid erythematous lesions with predominant acral localization as well as histological findings...
January 19, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29352101/activation-of-disease-during-therapy-with-alemtuzumab-in-3-patients-with-multiple-sclerosis
#3
Thomas Wehrum, Lena-Alexandra Beume, Oliver Stich, Irina Mader, Mathias Mäurer, Adam Czaplinski, Cornelius Weiller, Sebastian Rauer
OBJECTIVE: To report 3 patients with multiple sclerosis showing severe activation of disease during immunotherapy with alemtuzumab. METHODS: Retrospective case series. RESULTS: Patient 1, a 21-year-old woman, developed severe cognitive impairment, sight deterioration, severe gait ataxia, urinary retention, and extensive progression of cerebral lesion load, including new lesions that exhibited gadolinium ring enhancement and dominance of CD19/20-positive B lymphocytes, 6 months after induction of alemtuzumab...
January 19, 2018: Neurology
https://www.readbyqxmd.com/read/29350789/tcr-modifications-that-enhance-chain-pairing-in-gene-modified-t-cells-can-augment-cross-reactivity-and-alleviate-cd8-dependence
#4
Timothy T Spear, Kendra C Foley, Elizabeth Garrett-Mayer, Michael I Nishimura
T cell receptor (TCR) gene-modified T cells are a promising immunotherapy but require refinement to improve clinical responses and limit off-target toxicities. A variety of TCR and gene-delivery vector modifications have been developed to enhance introduced TCR expression and limit introduced/endogenous TCR chain mispairing, improving target antigen recognition and minimizing mispairing-induced cross-reactivity. Using our well-characterized HCV1406 TCR, we previously compared the impact of various chain pairing enhancing modifications on TCR expression and cognate antigen recognition...
January 19, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29350342/mesenchymal-stromal-cells-of-the-bone-marrow-and-natural-killer-cells-cell-interactions-and-cross-modulation
#5
Mehdi Najar, Mohammad Fayyad-Kazan, Nathalie Meuleman, Dominique Bron, Hussein Fayyad-Kazan, Laurence Lagneaux
Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are multipotent progenitor cells that have shown promise for several different therapeutic applications. As they are able to modulate the function of several types of immune cells, BM-MSCs are highly important in the field of cell-based immunotherapy. Understanding BM-MSC-natural killer (NK) cell interactions is crucial for improving their therapeutic efficiency. Here, we observed that the type of NK cell-activating cytokine (e.g., IL-2, IL-12, IL-15 and IL-21) strongly influenced the outcomes of their interactions with BM-MSCs...
January 19, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29350327/hypermutated-tumors-and-immune-checkpoint-inhibition
#6
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
https://www.readbyqxmd.com/read/29350320/ethical-implications-in-vaccine-pharmacotherapy-for-treatment-and-prevention-of-drug-of-abuse-dependence
#7
Anna Carfora, Paola Cassandro, Alessandro Feola, Francesco La Sala, Raffaella Petrella, Renata Borriello
Different immunotherapeutic approaches are in the pipeline for the treatment of drug dependence. "Drug vaccines" aim to induce the immune system to produce antibodies that bind to drugs and prevent them from inducing rewarding effects in the brain. Drugs of abuse currently being tested using these new approaches are opioids, nicotine, cocaine, and methamphetamine. In human clinical trials, "cocaine and nicotine vaccines" have been shown to induce sufficient antibody levels while producing few side effects. Studies in humans, determining how these vaccines interact in combination with their target drug, are underway...
January 19, 2018: Journal of Bioethical Inquiry
https://www.readbyqxmd.com/read/29350175/update-on-the-nephrotoxicity-of%C3%A2-novel%C3%A2-anticancer-agents%C3%A2
#8
Eliezer Zachary Nussbaum, Mark A Perazella
Anticancer drug-induced kidney disease is a problem commonly encountered by nephrologists. The number of medications employed by oncologists causing acute and chronic kidney injury as well as electrolyte and acid-base disturbances has increased significantly over the past several decades. While conventional chemotherapeutic drugs induce a number of kidney lesions, emergence of very effective and well-tolerated targeted therapies and novel immunotherapies has increased the occurrence of drug-induced acute and chronic kidney injury in cancer patients...
January 19, 2018: Clinical Nephrology
https://www.readbyqxmd.com/read/29350031/microbiota-regulated-outcomes-of-human-cancer-immunotherapy-via-the-pd-1-pd-l1-axis
#9
Jaymin Patel, Jason M Crawford
No abstract text is available yet for this article.
January 19, 2018: Biochemistry
https://www.readbyqxmd.com/read/29348890/adoptive-immunotherapy-shows-encouraging-benefit-on-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis
#10
Binghao Zhao, Wenxiong Zhang, Dongliang Yu, Jianjun Xu, Yiping Wei
Although adoptive immunotherapy (AIT) is a novel emerging target treatment for non-small cell lung cancer (NSCLC), its actual efficacy remains controversial. In this meta-analysis, we aimed to evaluate the efficacy of AIT for NSCLC. We systematically searched PubMed, the Cochrane Library, EMBASE, Medline, and Web of Science for relevant parallel randomized controlled trials (RCTs) and high-quality observation studies of AIT without any language restrictions. Two investigators reviewed all the texts and extracted information regarding overall survival rate (OS), progression-free survival rate (PFS), objective response rate (ORR), and disease control rate (DCR) from eligible studies; sensitivity analyses and subgroup analyses were also conducted to reduce heterogeneity Of 319 suitable studies, 15 studies (13 RCTs and 2 observation studies) involving 1684 patients were finally included...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348866/protein-methyltransferases-and-demethylases-dictate-cd8-t-cell-exclusion-in-squamous-cell-carcinoma-of-the-head-and-neck
#11
Theodore Vougiouklakis, Riyue Bao, Yusuke Nakamura, Vassiliki Saloura
A subset of patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) benefit from pembrolizumab and nivolumab, but the majority of patients do not probably due to lack of activated cytotoxic CD8+ T-cells in their tumor tissues. Herein, we aim to investigate whether specific protein methyltransferases (PMTs) and demethylases (PDMTs) could play any roles in the CD8+ T-cell exclusion process in HPV-negative SCCHN. RNA sequencing data from the TCGA database were interrogated for HPV-negative SCCHN patients using a 10-gene chemokine signature that classifies SCCHN tissues into CD8+ T-cell inflamed and non-CD8+ T-cell inflamed phenotypes...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348865/targeting-t-cell-malignancies-using-anti-cd4-car-nk-92-cells
#12
Kevin G Pinz, Elizabeth Yakaboski, Alexander Jares, Hua Liu, Amelia E Firor, Kevin H Chen, Masayuki Wada, Huda Salman, William Tse, Nabil Hagag, Fengshuo Lan, Elaine Lai-Han Leung, Xun Jiang, Yupo Ma
Peripheral T-cell lymphomas (PTCLs) are a group of very aggressive non-Hodgkin's lymphomas (NHLs) with poor prognoses and account for a majority of T-cell malignancies. Overall, the standard of care for patients with T-cell malignancies is poorly established, and there is an urgent clinical need for a new approach. As demonstrated in B-cell malignancies, chimeric antigen receptor (CAR) immunotherapy provides great hope as a curative treatment regimen. Because PTCLs develop from mature T-cells, these NHLs are commonly CD4+, and CD4 is highly and uniformly expressed...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348685/overexpression-of-adhesion-molecules-and-barrier-molecules-is-associated-with-differential-infiltration-of-immune-cells-in-non-small-cell-lung-cancer
#13
Young Kwang Chae, Wooyoung M Choi, William H Bae, Jonathan Anker, Andrew A Davis, Sarita Agte, Wade T Iams, Marcelo Cruz, Maria Matsangou, Francis J Giles
Immunotherapy is emerging as a promising option for lung cancer treatment. Various endothelial adhesion molecules, such as integrin and selectin, as well as various cellular barrier molecules such as desmosome and tight junctions, regulate T-cell infiltration in the tumor microenvironment. However, little is known regarding how these molecules affect immune cells in patients with lung cancer. We demonstrated for the first time that overexpression of endothelial adhesion molecules and cellular barrier molecule genes was linked to differential infiltration of particular immune cells in non-small cell lung cancer...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348598/increased-diversity-with-reduced-diversity-evenness-of-tumor-infiltrating-t-cells-for-the-successful-cancer-immunotherapy
#14
Akihiro Hosoi, Kazuyoshi Takeda, Koji Nagaoka, Tamaki Iino, Hirokazu Matsushita, Satoshi Ueha, Shin Aoki, Kouji Matsushima, Masato Kubo, Teppei Morikawa, Kazutaka Kitaura, Ryuji Suzuki, Kazuhiro Kakimi
To facilitate the optimization of cancer immunotherapy lacking immune-related adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T-cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB, anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T-cells in the tumor were activated and expanded to a greater or lesser extent by these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD-1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB monotherapy...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348432/genome-wide-association-study-of-self-reported-food-reactions-in-japanese-identifies-shrimp-and-peach-specific-loci-in-the-hla-dr-dq-gene-region
#15
Seik-Soon Khor, Ryoko Morino, Kazuyuki Nakazono, Shigeo Kamitsuji, Masanori Akita, Maiko Kawajiri, Tatsuya Yamasaki, Azusa Kami, Yuria Hoshi, Asami Tada, Kenichi Ishikawa, Maaya Hine, Miki Kobayashi, Nami Kurume, Naoyuki Kamatani, Katsushi Tokunaga, Todd A Johnson
Food allergy is an increasingly important health problem in the world. Several genome-wide association studies (GWAS) focused on European ancestry samples have identified food allergy-specific loci in the HLA class II region. We conducted GWAS of self-reported reactivity with common foods using the data from 11011 Japanese women and identified shrimp and peach allergy-specific loci in the HLA-DR/DQ gene region tagged by rs74995702 (P = 6.30 × 10-17, OR = 1.91) and rs28359884 (P = 2.3 × 10-12, OR = 1...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348296/cart-targeting-of-solid-tumors-more-pieces-to-the-puzzle
#16
Michael Kalos
CART-based targeting of solid tumors remains a considerable and worthwhile challenge in the field of immunotherapy. The role of chemotherapy to target stroma and enhance CAR cell anti-tumor function, expansion and persistence is still unresolved.
January 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29346540/blood-and-lymphatic-vessels-contribute-to-the-impact-of-the-immune-microenvironment-on-clinical-outcome-in-non-small-cell-lung-cancer
#17
Giovanna Armani, Denise Madeddu, Giulia Mazzaschi, Giovanni Bocchialini, Francesco Sogni, Caterina Frati, Bruno Lorusso, Angela Falco, Costanza Annamaria Lagrasta, Stefano Cavalli, Chiara Mangiaracina, Rocchina Vilella, Gabriella Becchi, Letizia Gnetti, Emilia Corradini, Eugenio Quaini, Konrad Urbanek, Matteo Goldoni, Paolo Carbognani, Luca Ampollini, Federico Quaini
OBJECTIVES: Lymphangiogenesis plays a critical role in the immune response, tumour progression and therapy effectiveness. The aim of this study was to determine whether the interplay between the lymphatic and the blood microvasculature, tumour-infiltrating lymphocytes and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint constitutes an immune microenvironment affecting the clinical outcome of patients with non-small-cell lung cancer. METHODS: Samples from 50 squamous cell carcinomas and 42 adenocarcinomas were subjected to immunofluorescence to detect blood and lymphatic vessels...
January 15, 2018: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/29346301/braf-and-mek-inhibitors-influence-the-function-of-reprogrammed-t-cells-consequences-for-adoptive-t-cell-therapy
#18
Jan Dörrie, Lek Babalija, Stefanie Hoyer, Kerstin F Gerer, Gerold Schuler, Lucie Heinzerling, Niels Schaft
BRAF and MEK inhibitors (BRAFi/MEKi), the standard treatment for patients with BRAFV600 mutated melanoma, are currently explored in combination with various immunotherapies, notably checkpoint inhibitors and adoptive transfer of receptor-transfected T cells. Since two BRAFi/MEKi combinations with similar efficacy are approved, potential differences in their effects on immune cells would enable a rational choice for triple therapies. Therefore, we characterized the influence of the clinically approved BRAFi/MEKi combinations dabrafenib (Dabra) and trametinib (Tram) vs...
January 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29346215/challenges-and-perspectives-for-immunotherapy-in-adenocarcinoma-of-the-pancreas-the-cancer-immunity-cycle
#19
Markus Kieler, Matthias Unseld, Daniela Bianconi, Gerald Prager
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a devastating 5-year overall survival of only approximately 7%. Although just 4% of all malignant diseases are accounted to PDAC, it will become the second leading cause of cancer-related deaths before 2030. Immunotherapy has proven to be a promising therapeutic option in various malignancies such as melanoma, non-small cell lung cancer (NSCLC), microsatellite instability-high gastrointestinal cancer, urinary tract cancer, kidney cancer, and others...
February 2018: Pancreas
https://www.readbyqxmd.com/read/29346180/development-of-a-pd-l1-complementary-diagnostic-immunohistochemistry-assay-sp142-for-atezolizumab
#20
Bharathi Vennapusa, Brian Baker, Marcin Kowanetz, Jennifer Boone, Ina Menzl, Jean-Marie Bruey, Gregg Fine, Sanjeev Mariathasan, Ian McCaffery, Simonetta Mocci, Sandra Rost, Dustin Smith, Eslie Dennis, Szu-Yu Tang, Bita Damadzadeh, Espen Walker, Priti S Hegde, J Andrew Williams, Hartmut Koeppen, Zachary Boyd
Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non-small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues...
January 16, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
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