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Neuroblastoma immunotherapy

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https://www.readbyqxmd.com/read/28296062/bronchiectasis-following-treatment-for-high-risk-neuroblastoma-a-case-series
#1
Madeleine Adams, Heidi Traunecker, Iolo Doull, Rachel Cox
High-risk (HR) neuroblastoma remains a very challenging disease to treat and long-term cure is only possible with intensive, multimodal treatment including chemotherapy, high-dose therapy, radiotherapy, surgery, and immunotherapy. As a result, treatment-related morbidity and late effects are common in survivors. This report outlines a case series of six patients who developed a chronic productive cough following treatment for HR neuroblastoma. High-resolution computed tomography scanning confirmed the diagnosis of bronchiectasis...
March 10, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28145567/gd2-targeted-immunotherapy-and-potential-value-of-circulating-micrornas-in-neuroblastoma
#2
REVIEW
Sharareh Gholamin, Hamed Miezaei, Seyed-Mostafa Razavi, Seyed Mahdi Hassanian, Leila Saadatpour, Aria Masoudifar, Soodabeh ShahidSales, Amir Avan
Neuroblastoma (NB) with various clinical presentation is a known childhood malignancy. Despite significant progress in treatment of NB afflicted patients, high risk disease is usually associated with poor outcome, resulting in long-term survival of less that 50%. Known as a disease most commonly originated form the nerve roots, the variants involved in NB imitation and progression remain to be elucidated. The outcome of low to intermediate risk disease is favorable whereas the high risk NB disease with dismal prognosis, positing the necessity of novel approaches for early detection and prognostication of advanced disease...
February 1, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28142287/overview-and-recent-advances-in-the-treatment-of-neuroblastoma
#3
Sarah B Whittle, Valeria Smith, Erin Doherty, Sibo Zhao, Scott McCarty, Peter E Zage
Children with neuroblastoma have widely divergent outcomes, ranging from cure in >90% of patients with low risk disease to <50% for those with high risk disease. Recent research has shed light on the biology of neuroblastoma, allowing for more accurate risk stratification and treatment reduction in many cases, although newer treatment strategies for children with high-risk and relapsed neuroblastoma are needed to improve outcomes. Areas covered: Neuroblastoma epidemiology, diagnosis, risk stratification, and recent advances in treatment of both newly diagnosed and relapsed neuroblastoma...
March 15, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28121746/respiratory-difficulties-in-children-with-underlying-asthma-during-immunotherapy-for-high-risk-neuroblastoma
#4
Laura K Metrock, Muna Qayed, Dawn Simon, Thomas Cash, Michael G O'Connor, Shaina Johnson, Natia Esiashvili, Howard M Katzenstein
Treatment of high-risk neuroblastoma now includes antibody based antitumor immunotherapy as part of standard care. Although this therapy has resulted in dramatic improvements in survival, it is associated with significant side effects. Children with underlying respiratory issues, and in particular asthma, may be more susceptible to immunotherapy associated respiratory compromise and pulmonary complications. Early routine involvement of pulmonology care is warranted for these patients in an effort to allow maximal delivery of immunotherapy and minimize acute and long-term complications...
January 24, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28061552/the-role-of-nursing-professionals-in-the-management-of-patients-with-high-risk-neuroblastoma-receiving-dinutuximab-therapy
#5
Rita Secola, Araz Marachelian, Susan L Cohn, Bonnie Toy, Kathleen Neville, Meaghan Granger, Angela Brentlinger, Gina Martin
Neuroblastoma, an embryonic cancer of the sympathetic nervous system, is the most common extracranial solid tumor in childhood. Dinutuximab (formerly called ch14.18), a monoclonal antibody targeting the disialoganglioside GD2, has been shown to significantly improve survival rates in patients with high-risk neuroblastoma. However, the safe and effective use of dinutuximab therapy in these high-risk patients requires medical expertise in patient selection, treatment administration, and the monitoring and management of adverse events...
January 1, 2017: Journal of Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses
https://www.readbyqxmd.com/read/28011498/metastatic-pattern-of-stage-iv-colorectal-cancer-with-high-frequency-microsatellite-instability-as-a-prognostic-factor
#6
Kenji Fujiyoshi, Gou Yamamoto, Takashi Takenoya, Akemi Takahashi, Yoshiko Arai, Mina Yamada, Miho Kakuta, Kensei Yamaguchi, Yoshito Akagi, Yoji Nishimura, Hirohiko Sakamoto, Kiwamu Akagi
BACKGROUND: A recent clinical trial on the immune check-point inhibitor pembrolizumab demonstrated that microsatellite instability (MSI) is a good biomarker for response to this inhibitor. However, clinicopathological features of advanced colorectal cancer (CRC) with high-frequency MSI (MSI-H) are unclear. PATIENTS AND METHODS: A total of 2,439 surgically resected CRC tissues were analyzed for MSI status, and mutational status of V-Ki-Ras2 Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B (BRAF)...
2017: Anticancer Research
https://www.readbyqxmd.com/read/27999754/neuroblastoma-patients-with-high-affinity-fcgr2a-3a-and-stimulatory-kir-2ds2-treated-by-long-term-infusion-of-anti-gd2-antibody-ch14-18-cho-show-higher-adcc-levels-and-improved-event-free-survival
#7
Nikolai Siebert, Christian Jensen, Sascha Troschke-Meurer, Maxi Zumpe, Madlen Jüttner, Karoline Ehlert, Silke Kietz, Ina Müller, Holger N Lode
Polymorphisms in Fc-gamma-receptor (FCGR) genes as well as killer cell immunoglobulin-like receptor (KIR) and KIR ligand (KIRL) repertoires may influence antitumor effects of monoclonal antibodies (mAb). Here, we systematically analyzed high- and low-affinity FCGR2A and -3A genotypes as well as stimulating and inhibitory KIR/KIRL combinations in 53 neuroblastoma (NB) patients treated by long-term infusion (LTI) of anti-GD2 IgG1 Ab ch14.18/CHO using validated real-time PCR methods. Patients with high-affinity FCGR2A and -3A genotypes showed a higher level of Ab-dependent cell-mediated cytotoxicity (ADCC) on day 8 after the start of ch14...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27830764/neuroblastoma
#8
Katherine K Matthay, John M Maris, Gudrun Schleiermacher, Akira Nakagawara, Crystal L Mackall, Lisa Diller, William A Weiss
Neuroblastoma is the most common extracranial solid tumour occurring in childhood and has a diverse clinical presentation and course depending on the tumour biology. Unique features of these neuroendocrine tumours are the early age of onset, the high frequency of metastatic disease at diagnosis and the tendency for spontaneous regression of tumours in infancy. The most malignant tumours have amplification of the MYCN oncogene (encoding a transcription factor), which is usually associated with poor survival, even in localized disease...
November 10, 2016: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/27826115/prussian-blue-nanoparticle-based-photothermal-therapy-combined-with-checkpoint-inhibition-for-photothermal-immunotherapy-of-neuroblastoma
#9
Juliana Cano-Mejia, Rachel A Burga, Elizabeth E Sweeney, John P Fisher, Catherine M Bollard, Anthony D Sandler, Conrad Russell Y Cruz, Rohan Fernandes
We describe "photothermal immunotherapy," which combines Prussian blue nanoparticle (PBNP)-based photothermal therapy (PTT) with anti-CTLA-4 checkpoint inhibition for treating neuroblastoma, a common, hard-to-treat pediatric cancer. PBNPs exhibit pH-dependent stability, which makes them suitable for intratumorally-administered PTT. PBNP-based PTT is able to lower tumor burden and prime an immune response, specifically an increased infiltration of lymphocytes and T cells to the tumor area, which is complemented by the antitumor effects of anti-CTLA-4 immunotherapy, providing a more durable treatment against neuroblastoma in an animal model...
November 5, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27756784/tgf%C3%AE-r1-blockade-with-galunisertib-ly2157299-enhances-anti-neuroblastoma-activity-of-the-anti-gd2-antibody-dinutuximab-ch14-18-with-natural-killer-cells
#10
Hung C Tran, Zesheng Wan, Michael A Sheard, Jianping Sun, Jeremy R Jackson, Jemily Malvar, Yibing Xu, Larry Wang, Richard Sposto, Eugene S Kim, Shahab Asgharzadeh, Robert C Seeger
PURPOSE: Immunotherapy of high-risk neuroblastoma using the anti-GD2 antibody dinutuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC). Galunisertib, an inhibitor of TGFβR1, was examined for its ability to enhance the efficacy of dinutuximab in combination with human ex vivo activated NK (aNK) cells against neuroblastoma. EXPERIMENTAL DESIGN: TGFB1 and TGFBR1 mRNA expression was determined for 249 primary neuroblastoma tumors by microarray analysis...
February 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27716850/efficient-killing-of-high-risk-neuroblastoma-using-natural-killer-cells-activated-by-plasmacytoid-dendritic-cells
#11
Martine Cordeau, Assila Belounis, Martin Lelaidier, Paulo Cordeiro, Hervé Sartelet, Sabine Herblot, Michel Duval
High-risk neuroblastoma (NB) remains a major therapeutic challenge despite the recent advent of disialoganglioside (GD2)-antibody treatment combined with interleukin (IL)-2 and granulocyte monocyte-colony stimulating factor (GM-CSF). Indeed, more than one third of the patients still die from this disease. Here, we developed a novel approach to improve the current anti-GD2 immunotherapy based on NK cell stimulation using toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDCs). We demonstrated that this strategy led to the efficient killing of NB cells...
2016: PloS One
https://www.readbyqxmd.com/read/27708204/evidence-for-the-efficacy-of-immunotherapy-in-children-with-high-risk-neuroblastoma
#12
Elwira Szychot, Jarosław Peregud-Pogorzelski, Paweł Wawryków, Andrzej Brodkiewicz
Neuroblastoma is the most common extra-cranial malignancy of childhood, with the highest incidence in children younger than 4 years. The prognosis depends on many factors, such as age at diagnosis, stage of disease and molecular genetic subtype. More than 50% of children who present with the disease are deemed to have high-risk neuroblastoma. The standard therapy for children with high-risk neuroblastoma consists of intensive chemotherapy, surgery, radiotherapy, myeloablative consolidation with autologous haematopoietic stem cell rescue followed by the treatment of minimal residual disease with 13-cis-retinoic acid...
September 28, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/27684826/in-vivo-expansion-and-activation-of-%C3%AE-%C3%AE-t-cells-as-immunotherapy-for-refractory-neuroblastoma-a-phase-1-study
#13
Joseph G Pressey, Julia Adams, Lualhati Harkins, David Kelly, Zhiying You, Lawrence S Lamb
INTRODUCTION: CD3+ γδ+ T cells comprise 2% to 5% of circulating T cells with Vγ9Vδ2+ cells the dominant circulating subtype. Vγ9Vδ2+ cells recognize non-peptide phosphoantigens and stress-associated NKG2D ligands expressed on malignant cells. Strategies that incorporate the tumoricidal properties of γδ T cells represent a promising immunotherapeutic strategy for treatment of solid malignancies including neuroblastoma (NB). In this prospective, non-randomized Phase I trial, we assessed whether circulating Vγ9Vδ2+ cells could be safely expanded using intravenous ZOL (Zoledronate [Zometa]) and subcutaneous Interleukin-2 (IL-2) in patients with refractory NB...
September 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27637889/safe-and-effective-treatment-of-experimental-neuroblastoma-and-glioblastoma-using-systemically-delivered-triple-microrna-detargeted-oncolytic-semliki-forest-virus
#14
Mohanraj Ramachandran, Di Yu, Matheus Dyczynski, Sathishkumar Baskaran, Lei Zhang, Aleksei Lulla, Valeria Lulla, Sirle Saul, Sven Nelander, Anna Dimberg, Andres Merits, Justyna Leja-Jarblad, Magnus Essand
Background: Glioblastoma multiforme and high-risk neuroblastoma are cancers with poor outcome. Immunotherapy in the form of neurotropic oncolytic viruses is a promising therapeutic approach for these malignancies. Here we evaluate the oncolytic capacity of the neurovirulent and partly IFNβ-resistant Semliki Forest virus (SFV)-4 in glioblastoma multiformes and neuroblastomas. To reduce neurovirulence we constructed SFV4miRT, which is attenuated in normal central nervous system (CNS) cells through insertion of microRNA target sequences for miR124, miR125, miR134...
March 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27622013/the-proto-oncogene-myc-drives-expression-of-the-nk-cell-activating-nkp30-ligand-b7-h6-in-tumor-cells
#15
Sonja Textor, Felicitas Bossler, Kai-Oliver Henrich, Moritz Gartlgruber, Julia Pollmann, Nathalie Fiegler, Annette Arnold, Frank Westermann, Nina Waldburger, Kai Breuhahn, Sven Golfier, Mathias Witzens-Harig, Adelheid Cerwenka
Natural Killer (NK) cells are innate effector cells that are able to recognize and eliminate tumor cells through engagement of their surface receptors. NKp30 is a potent activating NK cell receptor that elicits efficient NK cell-mediated target cell killing. Recently, B7-H6 was identified as tumor cell surface expressed ligand for NKp30. Enhanced B7-H6 mRNA levels are frequently detected in tumor compared to healthy tissues. To gain insight in the regulation of expression of B7-H6 in tumors, we investigated transcriptional mechanisms driving B7-H6 expression by promoter analyses...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27507584/alterations-of-glycosphingolipids-in-embryonic-stem-cell-differentiation-and-development-of-glycan-targeting-cancer-immunotherapy
#16
Alice L Yu, Jung-Tung Hung, Ming-Yi Ho, John Yu
All mammalian cells display an array of surface glycans that can modulate cellular interactions and regulate the development of an organism. In spite of their important implications in health and disease, investigations of glycans pose a great challenge given their inherent heterogeneity and the frequently observed cross-reactivities of antibodies against glycosphingolipids (GSLs) with multiple glycans, which may lead to erroneous interpretation and conclusion. We employed matrix-assisted laser desorption-ionization mass spectrometry and tandem MS/MS analyses to systematically delineate changes in GSLs during differentiation of human embryonic stem (ES) and induced pluripotent stem cells into various derivatives...
August 9, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27485082/anti-gd2-mabs-and-next-generation-mab-based-agents-for-cancer-therapy
#17
Zulmarie Perez Horta, Jacob L Goldberg, Paul M Sondel
Tumor-specific monoclonal antibodies (mAbs) have demonstrated efficacy in the clinic, becoming an important approach for cancer immunotherapy. Due to its limited expression on normal tissue, the GD2 disialogangloside expressed on neuroblastoma cells is an excellent candidate for mAb therapy. In 2015, dinutuximab (an anti-GD2 mAb) was approved by the US FDA and is currently used in a combination immunotherapeutic regimen for the treatment of children with high-risk neuroblastoma. Here, we review the extensive preclinical and clinical development of anti-GD2 mAbs and the different mechanisms by which they mediate tumor cell killing...
September 2016: Immunotherapy
https://www.readbyqxmd.com/read/27471639/anti-gd2-mab-and-vorinostat-synergize-in-the-treatment-of-neuroblastoma
#18
Michiel Kroesen, Christian Büll, Paul R Gielen, Ingrid C Brok, Inna Armandari, Melissa Wassink, Maaike W G Looman, Louis Boon, Martijn H den Brok, Peter M Hoogerbrugge, Gosse J Adema
Neuroblastoma (NBL) is a childhood malignancy of the sympathetic nervous system. For high-risk NBL patients, the mortality rate is still over 50%, despite intensive multimodal treatment. Anti-GD2 monoclonal antibody (mAB) in combination with systemic cytokine immunotherapy has shown clinical efficacy in high-risk NBL patients. Targeted therapy using histone deacetylase inhibitors (HDACi) is currently being explored in cancer treatment and already shows promising results. Using our recently developed transplantable TH-MYCN NBL model, we here report that the HDAC inhibitor Vorinostat synergizes with anti-GD2 mAb therapy in reducing NBL tumor growth...
June 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27456981/dinutuximab-a-novel-immunotherapy-in-the-treatment-of-pediatric-patients-with-high-risk-neuroblastoma
#19
Joy Bartholomew, Tanea Washington, Sharon Bergeron, Danelle Nielson, Jennifer Saggio, Lindsay Quirk
Therapy combining dinutuximab with granulocyte macrophage colony stimulating factor, interleukin 2, and isotretinoin has significant side effects; however, these complications are generally predictable and can be managed proactively.
July 25, 2016: Journal of Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses
https://www.readbyqxmd.com/read/27390347/preclinical-assessment-of-cd171-directed-car-t-cell-adoptive-therapy-for-childhood-neuroblastoma-ce7-epitope-target-safety-and-product-manufacturing-feasibility
#20
Annette Künkele, Agne Taraseviciute, Laura S Finn, Adam J Johnson, Carolina Berger, Olivia Finney, Cindy A Chang, Lisa S Rolczynski, Christopher Brown, Stephanie Mgebroff, Michael Berger, Julie R Park, Michael C Jensen
PURPOSE: The identification and vetting of cell surface tumor-restricted epitopes for chimeric antigen receptor (CAR)-redirected T-cell immunotherapy is the subject of intensive investigation. We have focused on CD171 (L1-CAM), an abundant cell surface molecule on neuroblastomas and, specifically, on the glycosylation-dependent tumor-specific epitope recognized by the CE7 monoclonal antibody. EXPERIMENTAL DESIGN: CD171 expression was assessed by IHC using CE7 mAb in tumor microarrays of primary, metastatic, and recurrent neuroblastoma, as well as human and rhesus macaque tissue arrays...
July 7, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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