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JOURNAL ARTICLE
Nils Florian Trautwein, Johannes Schwenck, Christian Seitz, Ferdinand Seith, Eduardo Calderón, Sebastian von Beschwitz, Stephan Singer, Gerald Reischl, Rupert Handgretinger, Jürgen Schäfer, Peter Lang, Bernd J Pichler, Johannes H Schulte, Christian la Fougère, Helmut Dittmann
Background: The tumor-associated disialoganglioside GD2 is a bona fide immunotherapy target in neuroblastoma and other childhood tumors, including Ewing sarcoma and osteosarcoma. GD2-targeting antibodies proved to be effective in neuroblastoma and GD2-targeting chimeric antigen receptors (CAR)- expressing T cells as well as natural killer T cells (NKTs) are emerging. However, assessment of intra- and intertumoral heterogeneity has been complicated by ineffective immunohistochemistry as well as sampling bias in disseminated disease...
2024: Theranostics
#22
JOURNAL ARTICLE
Hong Li, Jie Zhao, Jingwei Yang, Jingyan Tang, Ting Zhang, Hui Jiang, Jingbo Shao
OBJECTIVE: To characterize the epidemiological, clinical, and molecular features of bone marrow relapse in high-risk neuroblastoma (HR-NB) and to identify potential prognostic indicators and therapeutic approaches for this specific subset within the Shanghai pediatric oncology landscape. METHODS: A retrospective study was conducted on 256 patients diagnosed with stage 4 neuroblastoma at two major pediatric hospitals in Shanghai, China, between 2008 and 2018. Patient data was collected, including demographic information, treatment regimens, and outcomes...
2024: American Journal of Cancer Research
#23
REVIEW
Jun Yang
The "undruggable" MYC oncoproteins are deregulated in 70% human cancers. The approval of DFMO, an irreversible inhibitor of ornithine oxidase (ODC1) that is a direct transcriptional target of MYC, demonstrates that patients can benefit from targeting MYC activity via an indirect approach. However, the mechanism of action of DFMO needs further studies to understand how it works in post-immunotherapy neuroblastomas. Efforts to develop a more potent and safer drug to block MYC function will continue despite challenges...
March 2024: British Journal of Cancer
#24
JOURNAL ARTICLE
Shu-Wei Chou, Hsiu-Hao Chang
Metronomic chemotherapy refers to the consistent and regular administration of low-dose chemotherapeutic agents over an extended period, with minimal or no extended drug-free intervals. The effectiveness of metronomic chemotherapy is derived from its capacity to impede tumor angiogenesis and foster antitumor immune responses, rather than merely interrupting tumor cell mitosis. Metronomic chemotherapy has been applied in the treatment of neuroblastoma for decades, including patients with newly diagnosed high-risk neuroblastoma and relapsed or refractory neuroblastoma...
February 2, 2024: Cancer Letters
#25
JOURNAL ARTICLE
Thomas Eichholz, Florian Heubach, Anne-Marie Arendt, Christian Seitz, Ines B Brecht, Martin Ebinger, Tim Flaadt, Daniela Süsskind, Lisa Richter, Isabel Hülsenbeck, Leonie Zerweck, Sophia Göricke, Frank Paulsen, Frank Dombrowski, Christian Flotho, Stefan Schönberger, Petra Ketteler, Johannes Schulte, Peter Lang
BACKGROUND: GD2-directed immunotherapy is highly effective in the treatment of high-risk neuroblastoma (NB), and might be an interesting target also in other high-risk tumors. METHODS: The German-Austrian Retinoblastoma Registry, Essen, was searched for patients, who were treated with anti-GD2 monoclonal antibody (mAb) dinutuximab beta (Db) in order to evaluate toxicity, response and outcome in these patients. Additionally, we evaluated anti-GD2 antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in retinoblastoma cell lines in vitro...
January 19, 2024: Cancer Immunology, Immunotherapy: CII
#26
JOURNAL ARTICLE
Manas Sehgal, Sonali Priyadarshini Nayak, Sarthak Sahoo, Jason A Somarelli, Mohit Kumar Jolly
Neuroblastoma is the most frequent extracranial pediatric tumor and leads to 15% of all cancer-related deaths in children. Tumor relapse and therapy resistance in neuroblastoma are driven by phenotypic plasticity and heterogeneity between noradrenergic (NOR) and mesenchymal (MES) cell states. Despite the importance of this phenotypic plasticity, the dynamics and molecular patterns associated with these bidirectional cell-state transitions remain relatively poorly understood. Here, we analyze multiple RNA-seq datasets at both bulk and single-cell resolution, to understand the association between NOR- and MES-specific factors...
December 31, 2024: Cancer Biology & Therapy
#27
JOURNAL ARTICLE
Judith Wienke, Lindy L Visser, Waleed M Kholosy, Kaylee M Keller, Marta Barisa, Evon Poon, Sophie Munnings-Tomes, Courtney Himsworth, Elizabeth Calton, Ana Rodriguez, Ronald Bernardi, Femke van den Ham, Sander R van Hooff, Yvette A H Matser, Michelle L Tas, Karin P S Langenberg, Philip Lijnzaad, Anne L Borst, Elisa Zappa, Francisca J Bergsma, Josephine G M Strijker, Bronte M Verhoeven, Shenglin Mei, Amira Kramdi, Restuadi Restuadi, Alvaro Sanchez-Bernabeu, Annelisa M Cornel, Frank C P Holstege, Juliet C Gray, Godelieve A M Tytgat, Marijn A Scheijde-Vermeulen, Marc H W A Wijnen, Miranda P Dierselhuis, Karin Straathof, Sam Behjati, Wei Wu, Albert J R Heck, Jan Koster, Stefan Nierkens, Isabelle Janoueix-Lerosey, Ronald R de Krijger, Ninib Baryawno, Louis Chesler, John Anderson, Hubert N Caron, Thanasis Margaritis, Max M van Noesel, Jan J Molenaar
Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. Since novel and improved immunotherapies may fill this need, we dissect the immunoregulatory interactions in neuroblastoma by single-cell RNA-sequencing of 24 tumors (10 pre- and 14 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas are infiltrated by natural killer (NK), T and B cells, and immunosuppressive myeloid populations...
February 12, 2024: Cancer Cell
#28
JOURNAL ARTICLE
Nadine Landolina, Francesca Romana Mariotti, Andrea Pelosi, Valentina D'Oria, Tiziano Ingegnere, Claudia Alicata, Paola Vacca, Lorenzo Moretta, Enrico Maggi
IL-37 is a member of the IL-1 superfamily exerting anti-inflammatory functions in a number of diseases. Extracellular IL-37 triggers the inhibitory receptor IL-1R8 that is known to regulate different NK cell pathways and functional activities including their anti-tumor effect. However, the effect of IL-37 on human NK cell functions is still to be unveiled. This study aimed to investigate the functional effect of IL-37 in human NK cells activated with IL-15. We found that IL-37 enhanced both NK cell cytotoxic activity against different tumor cell lines and cytokines production...
2024: Oncoimmunology
#29
JOURNAL ARTICLE
Elisa Landoni, Mark G Woodcock, Gabriel Barragan, Gabriele Casirati, Vincenzo Cinella, Simone Stucchi, Leah M Flick, Tracy A Withers, Hanna Hudson, Giulia Casorati, Paolo Dellabona, Pietro Genovese, Barbara Savoldo, Leonid S Metelitsa, Gianpietro Dotti
Human natural killer T cells (NKTs) are innate-like T lymphocytes increasingly used for cancer immunotherapy. Here we show that human NKTs expressing the pro-inflammatory cytokine interleukin-12 (IL-12) undergo extensive and sustained molecular and functional reprogramming. Specifically, IL-12 instructs and maintains a Th1-polarization program in NKTs in vivo without causing their functional exhaustion. Furthermore, using CD62L as a marker of memory cells in human NKTs, we observe that IL-12 maintains long-term CD62L-expressing memory NKTs in vivo...
January 2, 2024: Nature Communications
#30
JOURNAL ARTICLE
Guangfei Wang, Jinglin Wang, Ruxiang Du, Yi Wang, Zhiping Li
BACKGROUND: Anti-disialoganglioside (anti-GD2) monoclonal antibodies are effective immunotherapeutic drugs for treating neuroblastoma, yet their toxicity spectrum is unclear. OBJECTIVE: This study aimed to assess the toxicity profiles of three anti-GD2 monoclonal antibodies (dinutuximab, dinutuximab β, and naxitamab) in clinical applications by mining and evaluating the adverse drug reaction (ADR) signals from the US Food and Drug Administration Adverse Event Reporting System...
December 28, 2023: Paediatric Drugs
#31
JOURNAL ARTICLE
Sabina Kaczanowska, Tara Murty, Ahmad Alimadadi, Cristina F Contreras, Caroline Duault, Priyanka B Subrahmanyam, Warren Reynolds, Norma A Gutierrez, Reema Baskar, Catherine J Wu, Franziska Michor, Jennifer Altreuter, Yang Liu, Aashna Jhaveri, Vandon Duong, Hima Anbunathan, Claire Ong, Hua Zhang, Radim Moravec, Joyce Yu, Roshni Biswas, Stephen Van Nostrand, James Lindsay, Mina Pichavant, Elena Sotillo, Donna Bernstein, Amanda Carbonell, Joanne Derdak, Jacquelyn Klicka-Skeels, Julia E Segal, Eva Dombi, Stephanie A Harmon, Baris Turkbey, Bita Sahaf, Sean Bendall, Holden Maecker, Steven L Highfill, David Stroncek, John Glod, Melinda Merchant, Catherine C Hedrick, Crystal L Mackall, Sneha Ramakrishna, Rosandra N Kaplan
Chimeric antigen receptor T cells (CAR-Ts) have remarkable efficacy in liquid tumors, but limited responses in solid tumors. We conducted a Phase I trial (NCT02107963) of GD2 CAR-Ts (GD2-CAR.OX40.28.z.iC9), demonstrating feasibility and safety of administration in children and young adults with osteosarcoma and neuroblastoma. Since CAR-T efficacy requires adequate CAR-T expansion, patients were grouped into good or poor expanders across dose levels. Patient samples were evaluated by multi-dimensional proteomic, transcriptomic, and epigenetic analyses...
January 8, 2024: Cancer Cell
#32
JOURNAL ARTICLE
Mengjia Song, Yue Huang, Ye Hong, Juan Liu, Jia Zhu, Suying Lu, Juan Wang, Feifei Sun, Junting Huang, Jiaqian Xu, Yan Tang, Jian-Chuan Xia, Yizhuo Zhang
T/NK cell-based immunotherapy has achieved remarkable success in adult cancers but has limited efficacy in pediatric malignancies including high-risk neuroblastoma (NB). Immune defects of NB tumor microenvironment are poorly understood compared with adults. Here, we described the unique characteristics of NB immune contexture and determined the phenotype signatures of PD-L1-expressing CD8+ T and NK cells in NB tumors by systemically analyzing the spatial distribution of T and NK cells and the distinct expression of programmed death 1 (PD-1) and its ligand (PD-L1) in patients with NB...
2024: Oncoimmunology
#33
REVIEW
Jaume Mora, Shakeel Modak, Joyce Kinsey, Carolyn E Ragsdale, Hillard M Lazarus
Colony-stimulating factors have been shown to improve anti-disialoganglioside 2 (anti-GD2) monoclonal antibody response in high-risk neuroblastoma by enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). A substantial amount of research has focused on recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant to anti-GD2 monoclonal antibodies. There may be a disparity in care among patients as access to GM-CSF therapy and anti-GD2 monoclonal antibodies is not uniform...
April 15, 2024: International Journal of Cancer. Journal International du Cancer
#34
Amber K Weiner, Alexander B Radaoui, Matthew Tsang, Daniel Martinez, Simone Sidoli, Karina L Conkrite, Alberto Delaidelli, Apexa Modi, Jo Lynne Rokita, Khushbu Patel, Maria V Lane, Bo Zhang, Chuwei Zhong, Brian Ennis, Daniel P Miller, Miguel A Brown, Komal S Rathi, Pichai Raman, Jennifer Pogoriler, Tricia Bhatti, Bruce Pawel, Tina Glisovic-Aplenc, Beverly Teicher, Stephen W Erickson, Eric J Earley, Kristopher R Bosse, Poul H Sorensen, Kateryna Krytska, Yael P Mosse, Karin E Havenith, Francesca Zammarchi, Patrick H van Berkel, Malcolm A Smith, Benjamin A Garcia, John M Maris, Sharon J Diskin
UNLABELLED: Cancer immunotherapies have produced remarkable results in B-cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor specimens along with normal tissues to identify biologically relevant cell surface proteins that can serve as immunotherapeutic targets for neuroblastoma, an often-fatal childhood cancer of the developing nervous system. We apply this approach to human-derived cell lines (N=9) and cell/patient-derived xenograft (N=12) models of neuroblastoma...
December 8, 2023: bioRxiv
#35
REVIEW
Marjolein C Stip, Loes Teeuwen, Miranda P Dierselhuis, Jeanette H W Leusen, Daniëlle Krijgsman
Myeloid cells (granulocytes and monocytes/macrophages) play an important role in neuroblastoma. By inducing a complex immunosuppressive network, myeloid cells pose a challenge for the adaptive immune system to eliminate tumor cells, especially in high-risk neuroblastoma. This review first summarizes the pro- and anti-tumorigenic functions of myeloid cells, including granulocytes, monocytes, macrophages, and myeloid-derived suppressor cells (MDSC) during the development and progression of neuroblastoma. Secondly, we discuss how myeloid cells are engaged in the current treatment regimen and explore novel strategies to target these cells in neuroblastoma...
December 13, 2023: Journal of Experimental & Clinical Cancer Research: CR
#36
JOURNAL ARTICLE
Marco Ruella
Chimeric antigen receptor (CAR) T cell immunotherapy in solid cancer is severely limited by the absence of ideal targets. In this issue of Cancer Cell, Bergaggio et al. find that anaplastic lymphoma kinase (ALK) inhibitors can enhance the function of ALK-specific CAR T cells against neuroblastoma by increasing target density in cancer cells.
December 11, 2023: Cancer Cell
#37
JOURNAL ARTICLE
Muhammad Imran Qadir, Bilal Ahmed, Sumaira Noreen
Neuroblastoma is a malignant tumor of neuroblasts, immature nerve cells found in several areas of the body. It usually affects children under age of 5. As usual, the tumor has ability to grow rapidly and to expand vastly which ultimately leads to death. Mostly, management decisions can be drawn by the prediction of the stage of the disease as well as age at the time of its diagnosis. There are four main stages of neuroblastoma, and treatment is according to the low and high risk of the disease. Several cytotoxic agents along with other therapies (antibody therapy, gene therapy, and even immunological therapies, antiangiogenic therapy, etc...
2024: Critical Reviews in Eukaryotic Gene Expression
#38
JOURNAL ARTICLE
Lynn W Maines, Staci N Keller, Charles D Smith
Antibody-based cancer drugs that target the checkpoint proteins CTLA-4, PD-1 and PD-L1 provide marked improvement in some patients with deadly diseases such as lung cancer and melanoma. However, most patients are either unresponsive or relapse following an initial response, underscoring the need for further improvement in immunotherapy. Certain drugs induce immunogenic cell death (ICD) in tumor cells in which the dying cells promote immunologic responses in the host that may enhance the in vivo activity of checkpoint antibodies...
November 29, 2023: International Journal of Molecular Sciences
#39
JOURNAL ARTICLE
Yunyun Yang, Zhiyi Wan, Enli Zhang, Yingshi Piao
BACKGROUND: Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the olfactory mucosa. The paucity of genomic data has prevented the development of individualized ONB treatments. Here, we investigated the genomic and immune landscape of ONB in Chinese patients. METHODS: Whole exome sequencing (WES) and multiplex immunofluorescence (MIF) analysis were performed on tissue samples from 19 Chinese ONB patients. Patients were divided into low- and high-grade groups...
2023: Frontiers in Oncology
#40
REVIEW
Paul T Kennedy, Demetra Zannoupa, Meong Hi Son, Lekh N Dahal, John F Woolley
Neuroblastoma is the most frequent extracranial childhood tumour but effective treatment with current immunotherapies is challenging due to its immunosuppressive microenvironment. Efforts to date have focused on using immunotherapy to increase tumour immunogenicity and enhance anticancer immune responses, including anti-GD2 antibodies; immune checkpoint inhibitors; drugs which enhance macrophage and natural killer T (NKT) cell function; modulation of the cyclic GMP-AMP synthase-stimulator of interferon genes pathway; and engineering neuroblastoma-targeting chimeric-antigen receptor-T cells...
November 22, 2023: Journal for Immunotherapy of Cancer
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