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Neuroblastoma immunotherapy

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https://www.readbyqxmd.com/read/28780888/anti-gd2-immunotherapy-for-neuroblastomas
#1
Sameer Sait, Shakeel I Modak
Current therapeutic approaches for high-risk neuroblastoma (HR-NB) include high-dose chemotherapy, surgery and radiotherapy; interventions that are associated with long and short-term toxicities. Effective immunotherapy holds particular promise for improving survival and quality of life by reducing exposure to cytotoxic agents. GD2, a surface glycolipid is the most common target for immunotherapy. Areas covered: We review the status of anti-GD2 immunotherapies currently in clinical use for neuroblastomas and novel GD2-targeted strategies in preclinical development...
August 7, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28748630/transverse-myelitis-as-an-unexpected-complication-following-treatment-with-dinutuximab-in-pediatric-patients-with-high-risk-neuroblastoma-a-case-series
#2
Yang-Yang Ding, Jessica Panzer, John M Maris, Alicia Castañeda, Marta Gomez-Chiari, Jaume Mora
Immunotherapy with the anti-GD2 monoclonal antibody ch14.18, or dinutuximab, represents an important therapeutic advance in the treatment of pediatric high-risk neuroblastoma and is now considered part of standard of care in this patient population. To date, transverse myelitis as a result of dinutuximab therapy has not been reported in clinical trials or in the published literature. We describe three patients with clinical symptoms of transverse myelitis, confirmed via magnetic resonance imaging, shortly following initiation of dinutuximab...
July 27, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28733263/consolidation-therapy-for-newly-diagnosed-pediatric-patients-with-high-risk-neuroblastoma-using-busulfan-melphalan-autologous-hematopoietic-cell-transplantation-anti-gd2-antibody-granulocyte-macrophage-colony-stimulating-factor-interleukin-2-and-haploidentical
#3
Aimee C Talleur, Brandon M Triplett, Sara Federico, Ewelina Mamcarz, William Janssen, Jianrong Wu, David Shook, Wing Leung, Wayne L Furman
The treatment of pediatric high-risk neuroblastoma is intensive and multimodal. Despite the introduction of immunotherapy for minimal residual disease, survival rates remain suboptimal and new therapies are needed. As part of a phase 2 trial, we are using a consolidation therapy regimen that combines a busulfan/melphalan conditioning schema, autologous hematopoietic cell transplantation (AHCT), and experimental immunotherapy with hu14.18K322A (a humanized anti-GD2 monoclonal antibody), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-2, with or without the adoptive transfer of haploidentical natural killer cells (NKs)...
July 18, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28680756/amplification-of-n-myc-is-associated-with-a-t-cell-poor-microenvironment-in-metastatic-neuroblastoma-restraining-interferon-pathway-activity-and-chemokine-expression
#4
Julian P Layer, Marie T Kronmüller, Thomas Quast, Debby van den Boorn-Konijnenberg, Maike Effern, Daniel Hinze, Kristina Althoff, Alexander Schramm, Frank Westermann, Martin Peifer, Gunther Hartmann, Thomas Tüting, Waldemar Kolanus, Matthias Fischer, Johannes Schulte, Michael Hölzel
Immune checkpoint inhibitors have significantly improved the treatment of several cancers. T-cell infiltration and the number of neoantigens caused by tumor-specific mutations are correlated to favorable responses in cancers with a high mutation load. Accordingly, checkpoint immunotherapy is thought to be less effective in tumors with low mutation frequencies such as neuroblastoma, a neuroendocrine tumor of early childhood with poor outcome of the high-risk disease group. However, spontaneous regressions and paraneoplastic syndromes seen in neuroblastoma patients suggest substantial immunogenicity...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28680748/mycn-is-an-immunosuppressive-oncogene-dampening-the-expression-of-ligands-for-nk-cell-activating-receptors-in-human-high-risk-neuroblastoma
#5
Elisa Brandetti, Irene Veneziani, Ombretta Melaiu, Annalisa Pezzolo, Aurora Castellano, Renata Boldrini, Elisa Ferretti, Doriana Fruci, Lorenzo Moretta, Vito Pistoia, Franco Locatelli, Loredana Cifaldi
Neuroblastoma (NB) is the most common extracranial solid tumor occurring in childhood. Amplification of the MYCN oncogene is associated with poor prognosis. Downregulation on NB cells of ligands recognized by Natural Killer (NK) cell-activating receptors, involved in tumor cell recognition and lysis, may contribute to tumor progression and relapse. Here, we demonstrate that in human NB cell lines MYCN expression inversely correlates with that of ligands recognized by NKG2D and DNAM1 activating receptors in human NB cell lines...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28676342/tumor-antigen-and-receptor-densities-regulate-efficacy-of-a-chimeric-antigen-receptor-targeting-anaplastic-lymphoma-kinase
#6
Alec J Walker, Robbie G Majzner, Ling Zhang, Kelsey Wanhainen, Adrienne H Long, Sang M Nguyen, Paola Lopomo, Marc Vigny, Terry J Fry, Rimas J Orentas, Crystal L Mackall
We explored the utility of targeting anaplastic lymphoma kinase (ALK), a cell surface receptor overexpressed on pediatric solid tumors, using chimeric antigen receptor (CAR)-based immunotherapy. T cells expressing a CAR incorporating the single-chain variable fragment sequence of the ALK48 mAb linked to a 4-1BB-CD3ζ signaling domain lysed ALK-expressing tumor lines and produced interferon-gamma upon antigen stimulation but had limited anti-tumor efficacy in two xenograft models of human neuroblastoma. Further exploration demonstrated that cytokine production was highly dependent upon ALK target density and that target density of ALK on neuroblastoma cell lines was insufficient for maximal activation of CAR T cells...
July 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28659916/hla-bw4-i-80-isoform-differentially-influences-clinical-outcome-as-compared-to-hla-bw4-t-80-and-hla-a-bw4-isoforms-in-rituximab-or-dinutuximab-based-cancer-immunotherapy
#7
Amy K Erbe, Wei Wang, Patrick K Reville, Lakeesha Carmichael, KyungMann Kim, Eneida A Mendonca, Yiqiang Song, Jacquelyn A Hank, Wendy B London, Arlene Naranjo, Fangxin Hong, Michael D Hogarty, John M Maris, Julie R Park, M F Ozkaynak, Jeffrey S Miller, Andrew L Gilman, Brad Kahl, Alice L Yu, Paul M Sondel
Killer-cell immunoglobulin-like receptors (KIRs) are a family of glycoproteins expressed primarily on natural killer cells that can regulate their function. Inhibitory KIRs recognize MHC class I molecules (KIR-ligands) as ligands. We have reported associations of KIRs and KIR-ligands for patients in two monoclonal antibody (mAb)-based trials: (1) A Children's Oncology Group (COG) trial for children with high-risk neuroblastoma randomized to immunotherapy treatment with dinutuximab (anti-GD2 mAb) + GM-CSF + IL-2 + isotretinion or to treatment with isotretinoin alone and (2) An Eastern Cooperative Oncology Group (ECOG) trial for adults with low-tumor burden follicular lymphoma responding to an induction course of rituximab (anti-CD20 mAb) and randomized to treatment with maintenance rituximab or no-maintenance rituximab...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28651977/dexamethasone-intravenous-immunoglobulin-and-rituximab-combination-immunotherapy-for-pediatric-opsoclonus-myoclonus-syndrome
#8
Michael R Pranzatelli, Elizabeth D Tate
BACKGROUND: Although pulse-dose dexamethasone is increasingly favored for treating pediatric opsoclonus-myoclonus syndrome (OMS), and multimodal immunotherapy is associated with improved clinical response, there have been no neuroimmunologic studies of dexamethasone-based multimodal disease-modifying therapy. METHODS: In this observational retrospective study, 19 children with OMS (with or without associated neuroblastoma) underwent multibiomarker evaluation for neuroinflammation...
May 19, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28544814/optimization-of-liposomal-topotecan-for-use-in-treating-neuroblastoma
#9
Lina Chernov, Rebecca J Deyell, Malathi Anantha, Nancy Dos Santos, Roger Gilabert-Oriol, Marcel B Bally
The purpose of this work was to develop an optimized liposomal formulation of topotecan for use in the treatment of patients with neuroblastoma. Drug exposure time studies were used to determine that topotecan (Hycamtin) exhibited great cytotoxic activity against SK-N-SH, IMR-32 and LAN-1 neuroblastoma human cell lines. Sphingomyelin (SM)/cholesterol (Chol) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/Chol liposomes were prepared using extrusion methods and then loaded with topotecan by pH gradient and copper-drug complexation...
June 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28511709/incorporation-of-high-dose-131-i-metaiodobenzylguanidine-treatment-into-tandem-high-dose-chemotherapy-and-autologous-stem-cell-transplantation-for-high-risk-neuroblastoma-results-of-the-smc-nb-2009-study
#10
Ji Won Lee, Sanghoon Lee, Hee Won Cho, Youngeun Ma, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo, Eun Joo Cho, Suk-Koo Lee, Do Hoon Lim
BACKGROUND: In our previous SMC NB-2004 study of patients with high-risk neuroblastomas, which incorporated total-body irradiation (TBI) with second high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), the survival rate was encouraging; however, short- and long-term toxicities were significant. In the present SMC NB-2009 study, only TBI was replaced with (131)I-meta-iodobenzylguanidine (MIBG) treatment in order to reduce toxicities. METHODS: From January 2009 to December 2013, 54 consecutive patients were assigned to receive tandem HDCT/auto-SCT after nine cycles of induction chemotherapy...
May 16, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28479124/opsoclonus-myoclonus-syndrome-a-new-era-of-improved-prognosis
#11
Armine Galstyan, Colin Wilbur, Kathryn Selby, Juliette Hukin
BACKGROUND: Opsoclonus-myoclonus syndrome is an autoimmune neurological disorder characterized by opsoclonus, myoclonus, ataxia, and behavioral changes. Although long-term outcomes have historically been poor, including motor and cognitive disabilities, the advent of new and more aggressive immunotherapy regimens may be improving prognosis in opsoclonus-myoclonus syndrome. METHODS: We retrospectively reviewed the records of all children diagnosed with opsoclonus-myoclonus syndrome at BC Children's Hospital from 2000 to 2010...
July 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28465854/high-risk-neuroblastoma-with-metastases-to-bilateral-kidneys-at-diagnosis
#12
Toshihide Yoshikawa, Akihiko Tanizawa, Koji Suzuki, Kazumi Ikeda, Eishi Nomura, Yumekichi Maeda, Nanae Tanaka, Kenta Yamada, Yasuhiro Sakai, Yoshiaki Imamura, Yusei Ohshima
Renal metastasis at diagnosis with neuroblastoma is rare. We present a 14-month-old boy who was diagnosed with high-risk neuroblastoma with multiple metastases, including bilateral kidneys. He received five cycles of induction chemotherapy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation. All of the lesions shrank, and magnetic resonance imaging indicated that some of the metastases had disappeared. However, there were residual masses in the bilateral kidneys, and histological examination revealed the presence of tumor cells...
2017: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/28457491/chemoimmunotherapeutic-effect-of-combined-treatment-with-ex-vivo-generated-antigen-presenting-immune-cells-and-conventional-antitumor-agents-in-a-mouse-neuroblastoma-model
#13
Seiichiro Inoue, Yumiko Setoyama, Akio Odaka, Daiki Kitagawa, Yoshifumi Beck
PURPOSE: Combining antitumor immunotherapy with conventional intensive multimodal therapy may be considered for advanced neuroblastoma. We investigated combination therapy with ex vivo generated immunostimulatory cells and intraperitoneal doxorubicin. METHODS: Immunogenic death of neuro-2a neuroblastoma cells was induced by doxorubicin or cisplatin (negative control). Mouse bone marrow cells were cultured with granulocyte-macrophage colony-stimulating factor, followed by addition of doxorubicin-killed neuro-2a cells with or without interleukin-4 and/or CpG-oligodeoxynucleotide to induce immunostimulatory cells...
April 21, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28442918/targeting-the-pd-1-pathway-in-pediatric-solid-tumors-and-brain-tumors
#14
REVIEW
Lars M Wagner, Val R Adams
While remarkable advances have been made in the treatment of pediatric leukemia over the past decades, new therapies are needed for children with advanced solid tumors and high-grade brain tumors who fail standard chemotherapy regimens. Immunotherapy with immune checkpoint inhibitors acting through the programmed cell death-1 (PD-1) pathway has shown efficacy in some chemotherapy-resistant adult cancers, generating interest that these agents may also be helpful to treat certain refractory pediatric malignancies...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28389455/dinutuximab-for-maintenance-therapy-in-pediatric-neuroblastoma
#15
REVIEW
Lauren McGinty, Jill Kolesar
PURPOSE: The pharmacology, clinical efficacy, safety, dosage and administration, and role in therapy of dinutuximab for the treatment of high-risk pediatric neuroblastoma are reviewed. SUMMARY: Dinutuximab (Unituxin, United Therapeutics) is a novel monoclonal antibody recently approved for use in combination with granulocyte- macrophage colony-stimulating factor, interleukin-2, and isotretinoin for the treatment of pediatric patients with high-risk neuroblastoma...
April 15, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28367616/management-of-neuroblastoma-icmr-consensus-document
#16
REVIEW
Deepak Bansal, Sidharth Totadri, Girish Chinnaswamy, Sandeep Agarwala, Tushar Vora, Brijesh Arora, Maya Prasad, Gauri Kapoor, Venkatraman Radhakrishnan, Siddharth Laskar, Tanvir Kaur, G K Rath, Sameer Bakhshi
Neuroblastoma (NBL) is the most common extra-cranial solid tumor in childhood. High-risk NBL is considered challenging and has one of the least favourable outcomes amongst pediatric cancers. Primary tumor can arise anywhere along the sympathetic chain. Advanced disease at presentation is common. Diagnosis is established by tumor biopsy and elevated urinary catecholamines. Staging is performed using bone marrow and mIBG scan (FDG-PET/bone scan if mIBG unavailable or non-avid). Age, stage, histopathological grading, MYCN amplification and 11q aberration are important prognostic factors utilized in risk stratification...
June 2017: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/28341563/avoidance-of-on-target-off-tumor-activation-using-a-co-stimulation-only-chimeric-antigen-receptor
#17
Jonathan Fisher, Pierre Abramowski, Nisansala Dilrukshi Wisidagamage Don, Barry Flutter, Anna Capsomidis, Gordon Weng-Kit Cheung, Kenth Gustafsson, John Anderson
Chimeric antigen receptors (CARs) combine T cell activation with antibody-mediated tumor antigen specificity, bypassing the need for T cell receptor (TCR) ligation. A limitation of CAR technology is on-target off-tumor toxicity caused by target antigen expression on normal cells. Using GD2 as a model cancer antigen, we hypothesized that this could be minimized by using T cells expressing Vγ9Vδ2 TCR, which recognizes transformed cells in a major histocompatibility complex (MHC)-unrestricted manner, in combination with a co-stimulatory CAR that would function independently of the TCR...
May 3, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28296062/bronchiectasis-following-treatment-for-high-risk-neuroblastoma-a-case-series
#18
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
#19
Sharareh Gholamin, Hamed Mirzaei, 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
#20
REVIEW
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...
April 2017: Expert Review of Anticancer Therapy
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