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Neuroblastoma immunotherapy

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https://www.readbyqxmd.com/read/29327110/the-role-of-interleukin-2-all-trans-retinoic-acid-and-natural-killer-cells-surveillance-mechanisms-in-anti-gd2-antibody-therapy-in-neuroblastoma
#1
Rosa Nguyen, Jim Houston, Wing K Chan, David Finkelstein, Michael A Dyer
Although anti-disialoganglioside (GD2) antibodies are successfully used for neuroblastoma therapy, a third of patients with neuroblastoma experience treatment failure or serious toxicity. Various strategies have been employed in the clinic to improve antibody-dependent cell-mediated cytotoxicity (ADCC), such as the addition of interleukin (IL)-2 to enhance natural killer (NK) cell function, adoptive transfer of allogeneic NK cells to exploit immune surveillance, and retinoid-induced differentiation therapy...
January 11, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29299660/reduction-of-myeloid-derived-suppressor-cells-reinforces-the-anti-solid-tumor-effect-of-recipient-leukocyte-infusion-in-murine-neuroblastoma-bearing-allogeneic-bone-marrow-chimeras
#2
Isabelle Dierckx de Casterlé, Sabine Fevery, Omer Rutgeerts, Fariba Poosti, Sofie Struyf, Caroline Lenaerts, Mark Waer, An D Billiau, Ben Sprangers
Allogeneic hematopoietic stem cell transplantation is an emerging treatment option for solid tumors because of its capacity to elicit immune graft-versus-tumor effects. However, these are often limited and associated with GvHD. Adoptive recipient leukocyte infusion (RLI) was shown to enhance anti-tumor responses of allogeneic bone marrow transplantation in murine neuroblastoma (Neuro2A)-bearing chimeras. In contrast to the clinically used donor leukocyte infusion, the RLI anti-tumor effect-elicited by host-versus-graft lymphohematopoietic reactivity-does not cause GvHD; however, the tumor growth-inhibitory effect is incomplete, because overall survival is not prolonged...
January 3, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29274926/3-methoxytyramine-an-independent-prognostic-biomarker-that-associates-with-high-risk-disease-and-poor-clinical-outcome-in-neuroblastoma-patients
#3
I R N Verly, A B P van Kuilenburg, N G G M Abeling, S M I Goorden, M Fiocco, F M Vaz, M M van Noesel, C M Zwaan, G J L Kaspers, J H M Merks, H N Caron, G A M Tytgat
INTRODUCTION: Prognosis of neuroblastoma patients is very diverse, indicating the need for more accurate prognostic parameters. The excretion of catecholamine metabolites by most neuroblastomas is used for diagnostic purposes, but their correlation with prognosis has hardly been investigated. Therefore, we performed an in-depth analysis of a panel of elevated urinary catecholamine metabolites at diagnosis and their correlation with prognosis. PATIENTS AND METHODS: Retrospective study of eight urinary catecholamine metabolites in a test (n = 96) and validation (n = 205) cohort of patients with neuroblastoma (all stages) at diagnosis...
December 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29225605/the-state-of-cellular-adoptive-immunotherapy-for-neuroblastoma-and-other-pediatric-solid-tumors
#4
Thanh-Phuong Le, To-Ha Thai
Research on adult cancer immunotherapy is proceeding at a rapid pace resulting in an impressive success rate exemplified by a few high profile cases. However, this momentum is not readily extended to pediatric immunotherapy, and it is not for lack of trying. Though reasons for the slower advance are not apparent, some issues can be raised. Pediatric cancer patients represent a distinct demographic group whose immune system is inherently different from that of mature adults. Treating pediatric patients with immunotherapy designed for adults may not yield objective clinical responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29221128/mycn-amplified-stage-2-3-neuroblastoma-excellent-survival-in-the-era-of-anti-gd2-immunotherapy
#5
Brian H Kushner, Michael P LaQuaglia, Shakeel Modak, Suzanne L Wolden, Ellen M Basu, Stephen S Roberts, Kim Kramer, Karima Yataghene, Irene Y Cheung, Nai-Kong V Cheung
High-risk neuroblastoma (HR-NB) includes MYCN-amplified stage 2/3, but reports covering anti-GD2 immunotherapy, which recently became standard for HR-NB, do not provide details on this subset. We now report on all 20 MYCN-amplified stage 2/3 patients who received induction chemotherapy at our center during the era of consolidation with anti-GD2 antibody 3F8/ granulocyte-macrophage colony-stimulating factor (GM-CSF) (2000-2015). Early in this period, consolidation included autologous stem-cell transplantation (ASCT)...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207115/current-status-and-future-prospects-of-the-strategy-of-combining-car%C3%A2-t-with-pd%C3%A2-1-blockade-for-antitumor-therapy-review
#6
Jinjing Xu, Qing Zhang, Kang Tian, Haiyu Wang, Hong Yin, Junnian Zheng
The immune system serves an important role in controlling and eradicating malignant cells. Immunotherapy for treating tumors has received much attention in recent years due to its marked effect. There are two approaches which currently lead this field: Chimeric antigen receptor‑modified T‑cell immunotherapy (CAR‑T) and programmed cell death protein-1 blockade (PD‑1 blockade). CAR‑T has emerged as a promising regimen for the treatment of a range of types of cancer, including chronic lymphoid leukemia and neuroblastoma, with studies of long term remission in certain patients...
February 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29196189/pd-l1-inflammation-non-coding-rnas-and-neuroblastoma-immuno-oncology-perspective
#7
REVIEW
Palanisamy Nallasamy, Srinivas Chava, Sumit S Verma, Shruti Mishra, Santhi Gorantla, Don W Coulter, Siddappa N Byrareddy, Surinder K Batra, Subash C Gupta, Kishore B Challagundla
Neuroblastoma is the most common pediatric solid tumor of neural crest origin. The current treatment options for neuroblastoma produce severe side effects. Programmed death-ligand 1 (PD-L1), chronic inflammation, and non-coding RNAs are known to play a significant role in the pathogenesis of neuroblastoma. Cancer cells and the surrounding cells in the tumor microenvironment express PD-L1. Programmed death-1 (PD-1) is a co-receptor expressed predominantly by T cells. The binding of PD-1 to its ligands, PD-L1 or PD-L2, is vital for the physiologic regulation of the immune system...
November 28, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29191664/immune-reconstitution-following-autologous-stem-cell-transplantation-in-patients-with-high-risk-neuroblastoma-at-the-time-of-immunotherapy
#8
Michele L Nassin, Elitsa Nicolaou, Sandeep Gurbuxani, Susan L Cohn, John M Cunningham, James L LaBelle
Outcomes for patients with high-risk neuroblastoma (HR-NBL) are significantly improved with the addition of immunotherapy (dinutuximab + cytokines) following autologous hematopoietic stem cell transplantation (autoHSCT). We hypothesized that the immune system is not fully reconstituted at the initiation of immunotherapy. To test this hypothesis, we evaluated hematologic and immune subsets in thirty-four patients with HR-NBL before and following autoHSCT(s). We found that absolute T-, B-, and NK cell counts at the time of immunotherapy were below normal in 80% of patients...
November 27, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29189429/new-developments-in-immunotherapy-for-pediatric-solid-tumors
#9
Liora M Schultz, Robbie Majzner, Kara L Davis, Crystal Mackall
PURPOSE OF REVIEW: Building upon preclinical advances, we are uncovering immunotherapy strategies that are translating into improved outcomes in tumor subsets. Advanced pediatric solid tumors carry poor prognoses and resultant robust efforts to apply immunotherapy advances to pediatric solid tumors are in progress. Here, we discuss recent developments in the field using mAb and mAb-based therapies including checkpoint blockade and chimeric antigen receptors (CARs). RECENT FINDINGS: The pediatric solid tumor mAb experience targeting the diganglioside, GD2, for patients with neuroblastoma has been the most compelling to date...
November 20, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29180536/high-affinity-gd2-specific-car-t-cells-induce-fatal-encephalitis-in-a-preclinical-neuroblastoma-model
#10
Sarah A Richman, Selene Nunez-Cruz, Babak Moghimi, Lucy Z Li, Zachary T Gershenson, Zissimos Mourelatos, David M Barrett, Stephan A Grupp, Michael C Milone
The GD2 ganglioside, which is abundant on the surface of neuroblastoma cells, is targeted by an FDA-approved therapeutic monoclonal antibody and is an attractive tumor-associated antigen for cellular immunotherapy. Chimeric antigen receptor (CAR)-modified T cells can have potent antitumor activity in B-cell malignancies, and trials to harness this cytolytic activity toward GD2 in neuroblastoma are underway. In an effort to enhance the antitumor activity of CAR T cells that target GD2, we generated variant CAR constructs predicted to improve the stability and the affinity of the GD2-binding, 14G2a-based, single-chain variable fragment (scFv) of the CAR, and compared their properties in vivo...
November 27, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29123953/pd-1-blockade-augments-anti-neuroblastoma-immune-response-induced-by-anti-gd2-antibody-ch14-18-cho
#11
Nikolai Siebert, Maxi Zumpe, Madlen Jüttner, Sascha Troschke-Meurer, Holger N Lode
Immunotherapy with anti-GD2 antibody (Ab) ch14.18/CHO is effective for treatment of high-risk neuroblastoma (NB) patients and is mainly based on GD2-specific Ab-dependent cellular cytotoxicity (ADCC). Strategies to further enhance the efficacy are important and currently explored in prospective clinical trials randomizing ch14.18/CHO ± IL-2. Recently, expression of programmed death 1 (PD-1) inhibitory receptor by effector cells and its ligand (PD-L1) by tumor cells has been shown. Here, we report for the first time effects of PD-1 blockade on ch14...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29120699/tolerability-response-and-outcome-of-high-risk-neuroblastoma-patients-treated-with-long-term-infusion-of-anti-gd2-antibody-ch14-18-cho
#12
Ina Mueller, Karoline Ehlert, Stefanie Endres, Lena Pill, Nikolai Siebert, Silke Kietz, Penelope Brock, Alberto Garaventa, Dominique Valteau-Couanet, Evelyne Janzek, Norbert Hosten, Andreas Zinke, Winfried Barthlen, Emine Varol, Hans Loibner, Ruth Ladenstein, Holger N Lode
Immunotherapy with short term infusion (STI) of monoclonal anti-GD2 antibody (mAb) ch14.18 (4 × 25mg/m(2)/d; 8-20h) in combination with cytokines and 13-cis retinoic acid (RA) prolonged survival in high-risk neuroblastoma (NB) patients. Here, we investigated long-term infusion (LTI) of ch14.18 produced in Chinese hamster ovary cells (ch14.18/CHO; 10 × 10mg/m(2); 24h) in combination with subcutaneous (s.c.) interleukin-2 (IL-2) in a single center program and report clinical response, toxicity and survival...
November 9, 2017: MAbs
https://www.readbyqxmd.com/read/29103425/cancer-and-autoimmunity-paraneoplastic-neurological-disorders-associated-with-neuroblastic-tumors
#13
Wendy G Mitchell, Franz Blaes
Cancer and autoimmunity come together in paraneoplastic syndromes (PNS), which reflect the remote, not direct, effects of cancer. In the pediatric population, a variety of PNS have been described, but the most common of these rare disorders are instigated by neuroblastic tumors, such as neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. The main pediatric-onset neurological PNS are ROHHAD syndrome, anti-ANNA1 (anti-Hu), and opsoclonus-myoclonus syndrome. They manifest distinctive neurological features, which aid the diagnosis, though under-recognition still poses serious challenges and risks...
August 2017: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/29070883/combined-immunotherapy-with-anti-pdl-1-pd-1-and-anti-cd4-antibodies-cures-syngeneic-disseminated-neuroblastoma
#14
Valentina Rigo, Laura Emionite, Antonio Daga, Simonetta Astigiano, Maria Valeria Corrias, Concetta Quintarelli, Franco Locatelli, Silvano Ferrini, Michela Croce
Anti-PD-1 or anti-PD-L1 blocking monoclonal antibodies (mAbs) have shown potent anti-tumor effects in adult cancer patients and clinical studies have recently been started in pediatric cancers, including high-risk/relapsing neuroblastoma (NB). Therefore, we studied the effects of anti-PD-1/PD-L1 mAbs in two syngeneic models of disseminated NB generated by the injection of either Neuro2a or NXS2 cells, which express PD-L1. In addition, we tested the combination of these agents with the immune-enhancing cytokine IL-21, the Ecto-NTPDase inhibitor POM-1, an anti-CD25 mAb targeting Treg cells, or an anti-CD4 mAb...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29067879/expression-of-disialoganglioside-gd2-in-neuroblastic-tumors-a-prognostic-value-for-patients-treated-with-anti-gd2-immunotherapy
#15
Tatjana Terzic, Martine Cordeau, Sabine Herblot, Pierre Teira, Sonia Cournoyer, Mona Beaunoyer, Michel Peuchmaur, Michel Duval, Herve Sartelet
Neuroblastoma, a malignant neoplasm of the sympathetic nervous system, is one of the most aggressive pediatric cancers. Patients with stage IV high-risk neuroblastoma receive an intensive multimodal therapy ending with an immunotherapy based on a chimeric monoclonal antibody ch14.18. Although the use of ch14.18 monoclonal antibody has significantly increased the survival rate of high-risk neuroblastoma patients, about 33% of these patients still relapse and die from their disease. Ch14.18 targets the disialoganglioside, GD2, expressed on neuroblastic tumor (NT) cells...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/29062613/emerging-and-investigational-therapies-for-neuroblastoma
#16
Mark A Applebaum, Ami V Desai, Julia L Glade Bender, Susan L Cohn
INTRODUCTION: Treatment for children with clinically aggressive, high-risk neuroblastoma remains challenging. Less than 50% of patients with high-risk neuroblastoma will survive long-term with current therapies, and survivors are at risk for serious treatment-related late toxicities. Here, we review new and evolving treatments that may ultimately improve outcome for children with high-risk neuroblastoma with decreased potential for late adverse events. AREAS COVERED: New strategies for treating high-risk neuroblastoma are reviewed including: radiotherapy, targeted cytotoxics, biologics, immunotherapy, and molecularly targeted agents...
2017: Expert Opinion on Orphan Drugs
https://www.readbyqxmd.com/read/29061769/therapeutic-innovations-for-targeting-childhood-neuroblastoma-implications-of-the-neurokinin-1-receptor-system
#17
REVIEW
Michael Berger, Dietrich VON Schweinitz
Neuroblastoma is the most common solid extracranial malignant tumor in children. Despite recent advances in the treatment of this heterogenous tumor with surgery and chemotherapy, the prognosis in advanced stages remains poor. Interestingly, neuroblastoma is one of the few solid tumors, to date, in which an effect for targeted immunotherapy has been proven in controlled clinical trials, giving hope for further advances in the treatment of this and other tumors by targeted therapy. A large array of novel therapeutic options for targeted therapy of neuroblastoma is on the horizon...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29039999/treatment-and-survival-of-childhood-neuroblastoma-evidence-from-a-population-based-study-in-the-united-states
#18
Diarmuid Coughlan, Matthew Gianferante, Charles F Lynch, Jennifer L Stevens, Linda C Harlan
BACKGROUND: Childhood neuroblastoma describes a heterogeneous group of extracranial solid tumors, that are treated per risk profile. We sought to describe treatment patterns and survival using population-based data from throughout the United States. MATERIALS AND METHODS: Using the National Cancer Institute (NCI)'s Patterns of Care data, we analyzed treatment provided to newly diagnosed, histologically confirmed neuroblastoma patients in 2010 and 2011, registered to one of 14 Surveillance, Epidemiology, and End Results (SEER) cancer registries...
August 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/28972044/neuroblastoma-patients-kir-and-kir-ligand-genotypes-influence-clinical-outcome-for-dinutuximab-based-immunotherapy-a-report-from-the-children-s-oncology-group
#19
Amy K Erbe, Wei Wang, Lakeesha Carmichael, KyungMann Kim, Eneida A Mendonca, Yiqiang Song, Dustin Hess, Patrick K Reville, Wendy B London, Arlene Naranjo, Jacquelyn A Hank, Mitchell B Diccianni, Ralph A Reisfeld, Stephen D Gillies, Katherine K Matthay, Susan L Cohn, Michael D Hogarty, John M Maris, Julie R Park, Mehmet Fevzi Ozkaynak, Andrew Gilman, Alice L Yu, Paul M Sondel
PURPOSE: In 2010, a Children's Oncology Group (COG) phase III randomized trial for high-risk neuroblastoma patients (ANBL0032) demonstrated improved event-free survival (EFS) and overall survival (OS) following treatment with an immunotherapy regimen of dinutuximab, GM-CSF, IL-2, and isotretinoin compared to treatment with isotretinoin alone. Dinutuximab, a chimeric anti-GD2 monoclonal antibody, acts in part via NK cells. Killer Immunoglobulin-like Receptors (KIRs) on NK cells and their interactions with KIR-ligands can influence NK cell function...
October 2, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28959231/demographic-clinical-and-immunologic-features-of-389-children-with-opsoclonus-myoclonus-syndrome-a-cross-sectional-study
#20
Michael R Pranzatelli, Elizabeth D Tate, Nathan R McGee
Pediatric-onset opsoclonus-myoclonus syndrome (OMS) is a devastating neuroinflammatory, often paraneoplastic, disorder. The objective was to characterize demographic, clinical, and immunologic aspects in the largest cohort reported to date. Cross-sectional data were collected on 389 children in an IRB-approved, observational study at the National Pediatric Myoclonus Center. Non-parametric statistical analysis was used. OMS manifested in major racial/ethnic groups, paralleling US population densities. Median onset age was 1...
2017: Frontiers in Neurology
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