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JOURNAL ARTICLE
Sarah Aminov, Orsi Giricz, David T Melnekoff, R Alejandro Sica, Veronika Polishchuk, Cristian Papazoglu, Bonnie Yates, Hao-Wei Wang, Srabani Sahu, Yanhua Wang, Shanisha Gordon-Mitchell, Violetta V Leshchenko, Carolina Schinke, Kith Pradhan, Srinivas Aluri, Moah Sohn, Stefan K Barta, Beamon Agarwal, Mendel Goldfinger, Ioannis Mantzaris, Aditi Shastri, William Matsui, Ulrich Steidl, Joshua D Brody, Nirali N Shah, Samir Parekh, Amit Verma
While therapies targeting CD19 by antibodies, CAR-T cells and T cell engagers have improved the response rates in B-cell malignancies; the emergence of resistant cell populations with low CD19 expression can lead to relapsed disease. We developed an in vitro model of adaptive resistance facilitated by chronic exposure of leukemia cells to a CD19-immunotoxin. Single-cell (sc) RNAseq showed increase in transcriptionally distinct CD19low populations in resistant cells. Mass cytometry demonstrated that CD22 was also decreased in these CD19low resistant cells...
February 20, 2024: Journal of Clinical Investigation
#22
REVIEW
Adrian Kowalczyk, Julia Zarychta, Anna Marszołek, Joanna Zawitkowska, Monika Lejman
High-grade gliomas (HGG) account for approximately 10% of central nervous system (CNS) tumors in children and 25% of CNS tumors in adults. Despite their rare occurrence, HGG are a significant clinical problem. The standard therapeutic procedure in both pediatric and adult patients with HGG is the surgical resection of the tumor combined with chemotherapy and radiotherapy. Despite intensive treatment, the 5-year overall survival in pediatric patients is below 20-30%. This rate is even lower for the most common HGG in adults (glioblastoma), at less than 5%...
January 31, 2024: Cancers
#23
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
#24
JOURNAL ARTICLE
Kang An, Yan He, Yanjing Tang, Xiaoyan Gu, Juan Qian, Benshang Li
BACKGROUND: Development of secondary tumor after CART treatment is not well investigated. We report a pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient who developed histiocytic sarcoma shortly after CART therapy. CASE REPORT: A 9-year-old boy diagnosed with relapsed B-ALL presenting the KRAS A146T mutation received autologous mouse-derived CD19 and CD22 chimeric antigen receptor T-cell therapy at our center (Chinese Clinical Trial Registry: ChiCTR2000032211)...
January 31, 2024: International Journal of Hematology
#25
Timothy Shaw, Jessica Wagner, Liqing Tian, Elizabeth Wickman, Suresh Poudel, Jian Wang, Robin Paul, Selene Koo, Meifen Lu, Heather Sheppard, Yiping Fan, Francis O'Neil, Ching Lau, Xin Zhou, Jinghui Zhang, Stephen Gottschalk
Immunotherapy with CAR T cells for pediatric solid and brain tumors is constrained by available targetable antigens. Cancer-specific exons (CSE) present a promising reservoir of targets; however, these have not been explored and validated systematically in a pan-cancer fashion. To identify CSE targets, we analyzed 1,532 RNA-seq datasets from 16 types of pediatric solid and brain tumors for comparison with normal tissues using a newly developed workflow. We found 2,933 exons in 157 genes encoding proteins of the surfaceome or matrisome with high cancer specificity either at the gene (n=148) or the alternatively spliced (AS) isoform (n=9) level...
January 5, 2024: Research Square
#26
REVIEW
Ugo Testa, Simona Sica, Elvira Pelosi, Germana Castelli, Giuseppe Leone
Treatment of refractory and relapsed (R/R) B acute lymphoblastic leukemia (B-ALL) is an unmet medical need in both children and adults. Studies carried out in the last two decades have shown that autologous T cells engineered to express a chimeric antigen receptor (CAR-T) represent an effective technique for treating these patients. Antigens expressed on B-cells, such as CD19, CD20, and CD22, represent targets suitable for treating patients with R/R B-ALL. CD19 CAR-T cells induce a high rate (80-90%) of complete remissions in both pediatric and adult R/R B-ALL patients...
2024: Mediterranean Journal of Hematology and Infectious Diseases
#27
JOURNAL ARTICLE
Alex Hoover, Paige Reimche, Dave Watson, Lynn Tanner, Laura Gilchrist, Mike Finch, Yoav H Messinger, Lucie M Turcotte
BACKGROUND: B-lineage acute lymphoblastic leukemia (B-ALL) is the most common malignancy of childhood. With the introduction of novel cellular therapies, cost of care is a critical component and the financial burden experienced by patients and society requires evaluation. AIMS: This study aims to assess the utilization and cost of care for chimeric antigen receptor T-cell (CAR-T) therapy for pediatric ALL patients with commercial insurance coverage in the United States...
January 13, 2024: Cancer reports
#28
EDITORIAL
Peter Bader, Laura M Moser
No abstract text is available yet for this article.
December 26, 2023: Translational Pediatrics
#29
JOURNAL ARTICLE
L L An, D F Zhao, R F Hou, H H Guan, H Yan, Y H Lin, C R Tong, T Wu, S Y Liu
Objective: To observe the treatment response of a two-dose regimen of inotuzumab ozogamicin (inotuzumab), a monoclonal antibody targeting CD22, for patients with heavily treated relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), including those failed or relapsed after chimeric antigen receptor (CAR) -T-cell therapy. Methods: Pediatric and adult patients who received two doses of inotuzumab and who were evaluated after inotuzumab treatment were included. Antibody infusions were performed between March 2020 and September 2022...
November 14, 2023: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
#30
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
#31
REVIEW
Alan Jhones Barbosa Assis, Brunna Letícia de Oliveira Santana, Ana Cristina Moura Gualberto, Fabio Pittella-Silva
Acute Lymphoblastic Leukemia (ALL) is the predominant hematological malignancy in pediatric populations, originating from B- or T-cell precursors within the bone marrow. The disease exhibits a high degree of heterogeneity, both at the molecular level and in terms of clinical presentation. A complex interplay between inherited and acquired genetic alterations contributes to disease pathogenesis, often resulting in the disruption of cellular functions integral to the leukemogenic process. The advent of CRISPR/Cas9 as a gene editing tool has revolutionized biological research, underscoring its potential to modify specific genomic loci implicated in cancer...
2023: Frontiers in Pharmacology
#32
JOURNAL ARTICLE
Hirotoshi Sakaguchi
The prognosis of B-cell acute lymphoblastic leukemia in children, adolescents, and young adults has improved significantly over the second half of the last century, with long-term survival rates reaching 90%, due to risk factor stratification and risk-adjusted treatment intensity. On the contrary, there are relapsed/refractory cases, and antibody-mediated immunotherapy and chimeric antigen receptor T-cell therapy are now being used in combination with conventional chemotherapy and allogeneic hematopoietic cell transplantation; the development of this treatment is expected...
2023: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
#33
REVIEW
Aimee C Talleur, Swati Naik, Stephen Gottschalk
CD19-specific chimeric antigen receptor (CAR) T-cell therapy has become an integral part of our treatment armamentarium for pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). However, despite initial remission rates of greater than 80%, durable remission occurs in only 40% to 50% of patients. In this review we summarize our current knowledge of the role of consolidative hematopoietic cell transplantation in the management of pediatric patients who achieved a minimal residual disease-negative complete response post CD19 CAR T-cell therapy...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
#34
REVIEW
David Shyr, Kara L Davis, Alice Bertaina
Hematopoietic stem cell transplantation (HSCT) represents a consolidated therapeutic strategy for high-risk pediatric acute lymphoblastic leukemia (ALL), offering the potential for curative treatment. This manuscript delves into the debate around the more universal application of HSCT for pediatric ALL in the modern era, considering the ubiquitous availability of suitable donors. In fact, despite significant advancements in chemotherapy, targeted therapy, and immunotherapy, a subset of pediatric patients with ALL with high-risk features or relapse continue to encounter poor prognostic outcomes...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
#35
JOURNAL ARTICLE
Jakob R Passweg, Helen Baldomero, Marc Ansari, Caroline Arber, Yves Chalandon, Michael Daskalakis, Miriam Diepold, Tamara Diesch-Furlanetto, Michel A Duchosal, Sabine Gerull, Tayfun Güngör, Dominik Heim, Felicitas Hitz, Andreas Holbro, Stavroula Masouridi-Levrat, Gayathri Nair, Urban Novak, Thomas Pabst, Christoph Renner, Georg Stussi, Dominik Schneidawind, Urs Schanz, Luciano Wannesson, Jörg P Halter
The Swiss Blood Stem Cell Transplantation and Cellular Therapy Group (SBST) leads a mandatory national registry for all hematopoietic stem cell transplants (HCT) and cellular therapies. After 25 years, information was available for 11,226 patients receiving an HCT (4031 allogeneic and 7195 autologous), including 925 pediatric patients. We compared patient characteristics and outcome by quinquennia 1997-2001, 2002-2006, 2007-2011, 2012-2016, and 2017-2021. There were numerous changes over time. Allogeneic transplant recipients became older (median age 33...
January 2024: Hematological Oncology
#36
REVIEW
Yonatan Diamond, Maddie Gilsenan, Stacie Shiqi Wang, Diane Hanna, Rachel Conyers, Theresa Cole, David Hughes, Jacqueline Fleming, Deborah Meyran, Claudia Toro, Vajiranee Malalasekera, Seong Lin Khaw, Gabrielle M Haeusler
BACKGROUND: CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy is transforming care for pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). There are limited pediatric-specific data concerning the infection risks associated with CD19 CAR-T therapy and the adequacy of current antimicrobial prophylaxis guidelines for these patients. METHODS: We describe the antimicrobial prophylaxis used and the types of infectious occurring in the first 100 days following CAR-T therapy for relapsed or refractory B-cell ALL in children and adolescents (≤18 years) at our centre...
December 2023: Transplant Infectious Disease: An Official Journal of the Transplantation Society
#37
Mohammed Al Amine El Farissi, Youness Dehneh, Amine Kada, Mohamed Dahamou, Mohamed Khoulali, Noureddine Oulali, Faycal Moufid
Anaplastic large cell lymphoma (ALCL) is a rare variety of non-Hodgkin lymphoma that primarily affects children and young adults and is caused by the fusion of the nucleophosmin 1 and ALK genes, which turns on several signalling pathways. Despite the fact that ALCL frequently affects lymph nodes and extranodal sites, involvement of the central nervous system (CNS) is quite uncommon, with symptoms like pain and fever. The spinal localization may result in neurological impairments. T1WI hypointense lesions with T2WI hyperintensity can be observed on MR images, while bone sequestra can be seen in CT scans...
January 2024: Radiology Case Reports
#38
REVIEW
Colleen Callahan, Lauren Haas, Laura Smith
The treatment landscape for pediatric cancers over the last 11 years has undergone a dramatic change, especially with relapsed and refractory B-cell acute lymphoblastic leukemia (ALL), due to the introduction of chimeric antigen receptor-T (CAR-T) cell therapy. Because of the success of CAR-T cell therapy in patients with relapsed and refractory B-cell ALL, this promising therapy is undergoing trials in multiple other pediatric malignancies. This article will focus on the introduction of CAR-T cell therapy in pediatric B-cell ALL and discuss past and current trials...
November 2023: Asia-Pacific Journal of Oncology Nursing
#39
REVIEW
Oula K Dagher, Avery D Posey
The advent of chimeric antigen receptor (CAR) T cell therapy has resulted in unprecedented long-term clearance of relapse/refractory hematological malignancies in both pediatric and adult patients. However, severe toxicities, such as cytokine release syndrome and neurotoxicity, associated with CAR T cells affect therapeutic utility; and treatment efficacies for solid tumors are still not impressive. As a result, engineering strategies that modify other immune cell types, especially natural killer (NK) cells have arisen...
December 2023: Nature Immunology
#40
JOURNAL ARTICLE
Claudia Rossig, Andrew D Pearson, Gilles Vassal, Nicole Scobie, Nick Bird, Patricia Blanc, H Josef Vormoor, Friso G Calkoen, Franco Locatelli, Francesca Del Bufalo, Susana Rives, Elad Jacoby, Adriana Balduzzi, Jean-Pierre Bourquin, André Baruchel
No abstract text is available yet for this article.
November 27, 2023: Journal of Clinical Oncology
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