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Jing Jie, Yixin Zhang, Hongyue Zhou, Xiaoyu Zhai, Nannan Zhang, Hongyan Yuan, Weihua Ni, Guixiang Tai
Mucin 1 ( MUC1 ), being an oncogene, is an attractive target in tumor immunotherapy. Maltose binding protein (MBP) is a potent built-in adjuvant to enhance protein immunogenicity. Thus, a recombinant MUC1 and MBP antitumor vaccine (M-M) was constructed in our laboratory. To enhance the antitumor immune activity of M-M, CpG oligodeoxynucleotides 1826 (CpG 1826), a toll-like receptor-9 agonist, was examined in this study as an adjuvant. The combination of M-M and CpG 1826 significantly inhibited MUC1 -expressing B16 cell growth and prolonged the survival of tumor-bearing mice...
March 20, 2018: International Journal of Molecular Sciences
Erin E Burke, Jonathan S Zager
Introduction Current treatment of advanced melanoma is rapidly changing with the introduction of new and effective therapies including systemic as well as locoregional therapies. An example of one such locoregional therapy is intralesional injection with talimogene laherparepvec (T-VEC). Areas Covered T-VEC has been shown in a number of studies to be an effective treatment for patients with stage IIIB, IIIC and IVM1a melanoma. In this article the effectiveness, pharmacokinetics and safety profile of TVEC is reviewed...
March 20, 2018: Expert Opinion on Drug Metabolism & Toxicology
Marian Christoph Neidert, Daniel Johannes Kowalewski, Manuela Silginer, Konstantina Kapolou, Linus Backert, Lena Katharina Freudenmann, Janet Kerstin Peper, Ana Marcu, Sophie Shih-Yüng Wang, Juliane Sarah Walz, Fabian Wolpert, Hans-Georg Rammensee, Reinhard Henschler, Katrin Lamszus, Manfred Westphal, Patrick Roth, Luca Regli, Stefan Stevanović, Michael Weller, Günter Eisele
Glioblastoma is the most frequent malignant primary brain tumor. In a hierarchical tumor model, glioblastoma stem-like cells (GSC) play a major role in tumor initiation and maintenance as well as in therapy resistance and recurrence. Thus, targeting this cellular subset may be key to effective immunotherapy. Here, we present a mass spectrometry-based analysis of HLA-presented peptidomes of GSC and glioblastoma patient specimens. Based on the analysis of patient samples (n = 9) and GSC (n = 3), we performed comparative HLA peptidome profiling against a dataset of normal human tissues...
March 20, 2018: Acta Neuropathologica
Sinem Civriz Bozdağ, Meltem Kurt Yüksel, Taner Demirer
Stem cells can be either totipotent, pluripotent, multipotent or unipotent. Totipotent cells have the capability to produce all cell types of the developing organism, including both embryonic and extraembryonic tissues. The Hematopoietic Stem Cells (HSC) are the first defined adult stem cells (ASC) that give rise to all blood cells and immune system. Use of HSCs for treatment of hematologic malignancies, which is also called bone marrow (BM) transplantation or peripheral blood stem cells (PBSC) transplantation is the pioneer of cellular therapy and translational research...
March 20, 2018: Advances in Experimental Medicine and Biology
Siambi Kikete, Li Luo, Beitian Jia, Li Wang, Gregory Ondieki, Yuhong Bian
Today, cancers pose a major public health burden. Although a myriad of cancer treatments are available, only a few have achieved clinical efficacy. This is partly attributed to cancers capability to evade host immunity by converting dendritic cells (DCs) from potent stimulators to negative modulators of immunity. Dendritic cell-based immunotherapy attempts to resolve this problem by manipulating the functional characteristics of DCs. Plant-derived polysaccharides (PDPs) can stimulate the maturation of DCs conferring on them the capacity to present internalised tumorigenic antigens to naïve T cells and subsequently priming T cells to eliminate tumours...
March 19, 2018: Cytotechnology
Qingxia Yao, Karl P Fischer, D Lorne Tyrrell, Klaus S Gutfreund
Programmed death-1 (PD-1), upon engagement by its ligands, programmed death ligand-1 (PD-L1) and programmed death ligand-2 (PD-L2), provides signals that attenuate adaptive immune responses. Here we describe the identification of the Pekin duck PD-L2 (duPD-L2) and its gene structure. The duPD-L2 cDNA encodes a 321 amino acid protein that has an amino acid identity of 76% and 35% with chicken and human PD-L2, respectively. Mapping of the duPD-L2 cDNA with duck genomic sequences revealed an exonic structure similar to that of the human P dcd1lg2 gene...
March 2018: Biochemistry and Biophysics Reports
Marc-Olivier Baradez, Daniela Biziato, Enas Hassan, Damian Marshall
Cell therapies offer unquestionable promises for the treatment, and in some cases even the cure, of complex diseases. As we start to see more of these therapies gaining market authorization, attention is turning to the bioprocesses used for their manufacture, in particular the challenge of gaining higher levels of process control to help regulate cell behavior, manage process variability, and deliver product of a consistent quality. Many processes already incorporate the measurement of key markers such as nutrient consumption, metabolite production, and cell concentration, but these are often performed off-line and only at set time points in the process...
2018: Frontiers in Medicine
Chuang Qu, Shuhui Gao, Hongwei Shao, Wenfeng Zhang, Huabben Bo, Xin Lu, Tianjiao Chen, Jing Kou, Yue Wang, Gui Si Chen, Shulin Huang, Han Shen
Cluster of differentiation (CD)147 is highly expressed in drug-resistant tumor cell lines and is involved in the formation of tumor drug resistance. Therefore, immunotherapy utilizing CD147 epitope peptides is a promising approach for the elimination of drug-resistant tumor cells. However, like most tumor-associated antigens (TAAs), CD147 belongs to the autoantigen category, and T cells that recognize high affinity, immunodominant epitopes from autoantigens are deleted though thymic negative selection. Furthermore, wild-type autoantigen peptides cannot effectively activate and expand T lymphocytes with lower affinity T cell receptors in vivo ...
April 2018: Oncology Letters
Qiongshu Li, Muyun Liu, Man Wu, Xin Zhou, Shaobin Wang, Yuan Hu, Youfu Wang, Yixin He, Xiaoping Zeng, Junhui Chen, Qubo Liu, Dong Xiao, Xiang Hu, Weibin Liu
Placenta-specific 1 (PLAC1), a novel cancer-testis antigen (CTA), is expressed in a number of different human malignancies. It is frequently produced in breast cancer, serving a function in tumorigenesis. Adoptive immunotherapy using T cell receptor (TCR)-engineered T cells against CTA mediates objective tumor regression; however, to the best of our knowledge, targeting PLAC1 using engineered T cells has not yet been attempted. In the present study, the cDNAs encoding TCRα- and β-chains specific for human leukocyte antigen (HLA)-A*0201-restricted PLAC1 were cloned from a cytotoxic T-lymphocyte, generated by in vitro by the stimulation of CD8+ T cells using autologous HLA-A2+ dendritic cells loaded with a PLAC1-specific peptide (p28-36, VLCSIDWFM)...
April 2018: Oncology Letters
Wei Zhang, Xinyan Xie, Huijing Mi, Jinwan Sun, Shaoxue Ding, Lijuan Li, Hui Liu, Huaquan Wang, Rong Fu, Zonghong Shao
Myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by ineffective hematopoiesis that lead to leukemia. Disorders of the immune system serve important functions in the pathophysiology and progression of this disease. Different levels or mechanisms of natural killer (NK) cells in patients with MDS have been measured in previous studies, making it challenging to understand the pathogenesis of NK cytotoxicity. The present study investigated the frequency of NK cell-mediated antibody-dependent cellular cytotoxicity and explored the function of NK cells by their activating receptors, inhibition signals, degranulation and cytotoxicity factors...
April 2018: Oncology Letters
Yiming Wang, Rena Ma, Fang Liu, Seul A Lee, Li Zhang
Blockade of programmed death 1 (PD-1) protein and its ligand programmed death ligand 1 (PD-L1) has been used as cancer immunotherapy in recent years, with the blockade of PD-1 being more widely used than blockade of PD-L1. PD-1 and PD-L1 blockade therapy showed benefits in patients with various types of cancer; however, such beneficial effects were seen only in a subgroup of patients. Improving the efficacy of PD-1 and PD-L1 blockade therapy is clearly needed. In this review, we summarize the recent studies on the effects of gut microbiota on PD-1 and PD-L1 blockade and discuss the new perspectives on improving efficacy of PD-1 and PD-L1 blockade therapy in cancer treatment through modulating gut microbiota...
2018: Frontiers in Immunology
Yifan Wang, Weiye Deng, Nan Li, Shinya Neri, Amrish Sharma, Wen Jiang, Steven H Lin
Since the approval of anti-CTLA4 therapy (ipilimumab) for late-stage melanoma in 2011, the development of anticancer immunotherapy agents has thrived. The success of many immune-checkpoint inhibitors has drastically changed the landscape of cancer treatment. For some types of cancer, monotherapy for targeting immune checkpoint pathways has proven more effective than traditional therapies, and combining immunotherapy with current treatment strategies may yield even better outcomes. Numerous preclinical studies have suggested that combining immunotherapy with radiotherapy could be a promising strategy for synergistic enhancement of treatment efficacy...
2018: Frontiers in Pharmacology
Pedro O Flores-Villanueva, Malathesha Ganachari, Heinner Guio, Jaime A Mejia, Julio Granados
Lung cancer is a leading cause of cancer-related death among both men and women in the United States, where non-small cell lung cancer accounts for ∼85% of lung cancer. Lung adenocarcinoma (ADC) is the major histologic subtype. The presence of actionable mutations prompts the use of therapies designed to specifically address the deleterious effects of those cancer-driving mutations; these therapies have already shown promise in cases carrying those actionable mutations (∼30%). Innovative therapeutic approaches are needed for the treatment of 70% of patients suffering from lung ADC...
March 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Tuan Hiep Tran, Thi Thu Phuong Tran, Hanh Thuy Nguyen, Cao Dai Phung, Jee-Heon Jeong, Martina H Stenzel, Sung Giu Jin, Chul Soon Yong, Duy Hieu Truong, Jong Oh Kim
Crosstalk among immune cells has attracted considerable attention with the advent of immunotherapy as a novel therapeutic approach for challenging diseases, especially cancer, which is the leading cause of mortality worldwide. Dendritic cells-the key antigen-presenting cells-play a pivotal role in immunological response by presenting exogenous epitopes to T cells, which induces the self-defense mechanisms of the body. Furthermore, nanotechnology has provided promising ways for diagnosing and treating cancer in the last decade...
March 16, 2018: International Journal of Pharmaceutics
Michael R Pranzatelli, Tyler J Allison, Elizabeth D Tate
INTRODUCTION: Flow cytometric cerebrospinal fluid (CSF) lymphocyte subset analysis has improved the diagnosis of neuroinflammation and identified multiple markers of inflammation in opsoclonus-myoclonus syndrome (OMS). The aim of this exploratory, retrospective study was to analyze the effect of immunotherapy on these markers to determine which agents are disease modifying. METHODS: Cross-sectional immunological observations were made in an IRB-approved case-control study, and patients were treated empirically...
March 5, 2018: European Journal of Paediatric Neurology: EJPN
Xue-Juan Bai, Hong-Min Li, You-Rong Yang, Jun-Xian Zhang, Yan Liang, Xue-Qiong Wu
Relapse of pulmonary tuberculosis (PTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis. Severe immunodeficiency or immune disorders may be the main reason for TB recurrence. This study aimed to quantify serum inflammatory cytokine and soluble adhesion molecule levels in Re-treated smear-positive PTB patients before and after re-anti-TB drug therapy. Serum samples were collected from 30 healthy controls and 215 Treated active PTB patients at baseline and 2, 4, and 6 months post-re-treatment...
March 16, 2018: Cytokine
Julia R Schneider, Deborah R Shatzkes, Stephen C Scharf, Tristan M Tham, Kay O Kulason, François-Alexandre Buteau, Michela Del Prete, Shamik Chakraborty, Todd A Anderson, Saeed Asiry, Jean-Mathieu Beauregard, David J Langer, Peter D Costantino, John A Boockvar
BACKGROUND AND IMPORTANCE: Olfactory neuroblastoma, also known as esthesioneuroblastoma (ENB), is a malignant neoplasm with an unpredictable behavior. Currently, the widely accepted treatment is inductive chemotherapy, with or without surgery, followed by radiotherapy. Since data on genetics and molecular alterations of ENB are lacking, there is no standard molecularly targeted therapy. However, ENB commonly expresses the somatostatin receptor (SSTR) that is also expressed by neuroendocrine tumors...
March 14, 2018: Operative Neurosurgery (Hagerstown, Md.)
M E Rodríguez-Ruiz, J L Perez-Gracia, I Rodríguez, C Alfaro, C Oñate, G Pérez, I Gil-Bazo, A Benito, S Inogés, A López-Diaz de Cerio, M Ponz-Sarvise, L Resano, P Berraondo, B Barbés, S Martin-Algarra, A Gúrpide, M F Sanmamed, C de Andrea, A M Salazar, I Melero
BACKGROUND: Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects. PATIENTS AND METHODS: In this two-cohort pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24h with poly-ICLC (Hiltonol), TNF-α and IFN-α...
March 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Qi-Feng He, Yong Xu, Jun Li, Zheng-Ming Huang, Xiu-Hui Li, Xiaochen Wang
Immunotherapies have emerged as the most promising area in cancer treatments in recent years. CD8+ T cells, as one of the primary effector cells of anticancer immunity, however, when infiltrating in cancer tissues, are generally in dysfunctional states termed T-cell exhaustion. Exhausted CD8+ T cells are characterized by impaired activity and proliferative ability, increased apoptotic rate and reduced production of effector cytokines. Such dysfunctional CD8+ T cells serve as a barrier in successful cancer elimination...
March 15, 2018: Briefings in Functional Genomics
Daniel Katzman, Daniel H Sterman
PURPOSE OF REVIEW: This review article describes current diagnostic and treatment modalities for malignant pleural mesothelioma (MPM). RECENT FINDINGS: Few randomized trials in MPM have demonstrated improved survival with current therapies. A randomized trial of first-line chemotherapy with and without bevacizumab in unresectable MPM is the only randomized trial of a new treatment regimen to demonstrate a survival benefit since cisplatin with pemetrexed became the standard of care for unresectable MPM in 2003...
March 16, 2018: Current Opinion in Pulmonary Medicine
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