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CAR-T cell therapy for the treatment of adult high-grade gliomas.

Treatment for malignant primary brain tumors, including glioblastoma, remains a significant challenge despite advances in therapy. CAR-T cell immunotherapy represents a promising alternative to conventional treatments. This review discusses the landscape of clinical trials for CAR-T cell therapy targeting brain tumors, highlighting key advancements like novel target antigens and combinatorial strategies designed to address tumor heterogeneity and immunosuppression, with the goal of improving outcomes for patients with these aggressive cancers.

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… GD2 Gangliosides are molecules composed of glycosphingolipids coated with sugar chains that are widely expressed in normal tissues. … Gangliosides: the double-edge sword of neuro-ectodermal derived tumors. Biomolecules 9 , 311 (2019). 105. Traylor, T. D. & Hogan, E. L. Gangliosides of human cerebral astrocytomas. J. Neurochem. 34 , 126–131 (1980). 106. Prapa, M. et al. …

Defining neuroblastoma: From origin to precision medicine.

Neuroblastoma (NB), a heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations occurring during development that contribute to NB. We discuss current treatment regimens, present and future directions for the identification of novel therapeutic metabolic targets, differentiation

Sphingolipid metabolism and hematologic disorders: current understanding and future directions.

Sphingolipids are not only key structural components of cell membranes but also serve as important signaling molecules, and their metabolic homeostasis is essential for the maintenance of cellular functions. In recent years, with the advancement of technologies such as metabolomics, studies have revealed that sphingolipid metabolic abnormalities are extensively involved in the occurrence and development of various hematological disorders, including immune thrombocytopenia, myeloproliferative neoplasms, graft-versus-host disease, hereditary hematological diseases, and hematologic malignancies.

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… Sphingolipid metabolism: fundamental biological functions Structure and classification of sphingolipids Sphingolipids are structurally divided into three main classes: sphingomyelin, cerebrosides (neutral glycosphingolipids), and gangliosides (acidic glycosphingolipids). … Gangliosides, for instance, enrich within lipid rafts and participate in receptor clustering and immune responses ( Takahashi et al., 2022 ; van der Haar Àvila et al., 2023 ). Notably, the function of a given sphingolipid species is highly context-dependent. …

MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment.

Among childhood cancers, neuroblastoma is the most diffuse solid tumor and the deadliest in children. While to date, the pathology has become progressively manageable with a significant increase in 5-year survival for its less aggressive form, high-risk neuroblastoma (HR-NB) remains a major issue with poor outcome and little survivability of patients. The staging system has also been improved to better fit patient needs and to administer therapies in a more focused manner in consideration of pathology features. New and improved therapies have been developed; nevertheless, low efficacy and high

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… Interestingly, neuroblastoma represents an exception; in fact, almost all tumorigenic cells show the expression of aberrant gangliosides [ 116 , 117 ]—such as disialoganglioside GD2—which are nearly absent in the majority of normal tissue [ 118 ]. … Gangliosides are sialic acid-containing glycolipids [ 119 ] that are able to stimulate the immune response, and their use in immunotherapy was demonstrated to improve the outcome in a patient with HR-NB [ 114 , 120 , 121 , 122 ]. …

The Therapeutic Potential of Secreted Factors from Dental Pulp Stem Cells for Various Diseases.

An alternative source of mesenchymal stem cells has recently been discovered: dental pulp stem cells (DPSCs), including deciduous teeth, which can thus comprise potential tools for regenerative medicine. DPSCs derive from the neural crest and are normally implicated in dentin homeostasis. The clinical application of mesenchymal stem cells (MSCs) involving DPSCs contains various limitations, such as high cost, low safety, and cell handling issues, as well as invasive sample collection procedures. Although MSCs implantation offers favorable outcomes on specific diseases, implanted MSCs cannot su

Trial watch: Immunostimulatory cytokines in cancer therapy.

Tumor-targeting immune responses provide a significant contribution to (when they do not entirely account for) the clinical activity of diverse antineoplastic regimens, encompassing not only a large panel of immunotherapeutic strategies but also conventional cytotoxic molecules, targeted anticancer agents and irradiation. In line with this notion, several approaches have been devised to elicit novel or boost existing anticancer immune responses, including the administration of immunomodulatory cytokines. Such a relatively unspecific intervention suffices to mediate clinical effects in (at leas

Monoclonal Gammopathy of Undetermined Significance (MGUS)-Not So Asymptomatic after All.

Monoclonal Gammopathy of Undetermined Significance (MGUS) is considered to be a benign precursor condition that may progress to a lymphoproliferative disease or multiple myeloma. Most patients do not progress to an overt condition, but nevertheless, MGUS is associated with a shortened life expectancy and, in a minority of cases, a number of co-morbid conditions that include an increased fracture risk, renal impairment, peripheral neuropathy, secondary immunodeficiency, and cardiovascular disease. This review aims to consolidate current evidence for the significance of these co-morbidities befo

Role of Ceramide from Glycosphingolipids and Its Metabolites in Immunological and Inflammatory Responses in Humans.

Glycosphingolipids (GSLs) are composed of hydrophobic ceramide and hydrophilic sugar chains. GSLs cluster to form membrane microdomains (lipid rafts) on plasma membranes, along with several kinds of transducer molecules, including Src family kinases and small G proteins. However, GSL-mediated biological functions remain unclear. Lactosylceramide (LacCer, CDw17) is highly expressed on the plasma membranes of human phagocytes and mediates several immunological and inflammatory reactions, including phagocytosis, chemotaxis, and superoxide generation. LacCer forms membrane microdomains with the Sr

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… Gangliosides and gangliosidoses: principles of molecular and metabolic pathogenesis The Journal of Neuroscience 2013 33 25 10195 10208 10.1523/jneurosci.0822-13.2013 2-s2.0-84879143450 23785136 PMC6618597 19 Platt F. M. … Guillain-Barré syndrome and anti-ganglioside antibodies: a clinician-scientist's journey Proceedings of the Japan Academy—Series B: Physical and Biological Sciences 2012 88 7 299 326 10.2183/pjab.88.299 2-s2.0-84867034919 PMC3422685 22850724 92 Diamond B. Honig G. Mader S. Brimberg L. Volpe B. T. …

Рефлексивный ГИЛЬЯЙН-БАРРЕ СИНДРОМ В ХОДЕ С АЗИМПТОМАТИЧЕСКИМ МНОГОЛЕМЕНТОМ МИЛОМЫ, С КОТОРЫМ БУДЕТ ОБРАЩАТЬСЯ С НИЗКИМ РИТЕКСИМАБОМ.

Несмотря на чрезвычайную редкость, синдром Гильен-Барре (ГБС) был признан неврологическим осложнением множественной миэломы с переменной реакцией на плазмеферез (PEX), иммуноглобулины (IVIG) и антимиеломную терапию. В настоящем документе сообщается о случае, когда пациентка с асимптоматической множественной миеломой (АММ), первоначально представлявшая себя как PEX- и IVIG-refractory GBS. После отказа PEX, IVIG и антимиеломатерапии (bortezomib, elphalan и padnison) пациент в конечном итоге успешно лечился ритуксимой с низкой дозой ().100 мг/м2 в неделю four Дозы). Насколько нам известно, это пе

Is dosing of therapeutic immunoglobulins optimal? A review of a three-decade long debate in europe.

The consumption of immunoglobulins (Ig) is increasing due to better recognition of antibody deficiencies, an aging population, and new indications. This review aims to examine the various dosing regimens and research developments in the established and in some of the relevant off-label indications in Europe. The background to the current regulatory settings in Europe is provided as a backdrop for the latest developments in primary and secondary immunodeficiencies and in immunomodulatory indications. In these heterogeneous areas, clinical trials encompassing different routes of administration,

Surrogate Biomarkers in Gene Therapy for Orphan Diseases: Validation, Application, and Regulatory Aspects.

The development of gene therapies for rare hereditary disorders is hindered by small patient cohorts, incomplete characterization of natural disease history, and the impracticality of conducting long-term clinical trials. Surrogate biomarkers-quantifiable indicators predictive of clinical outcomes-represent a promising strategy to accelerate the evaluation of therapeutic efficacy. This review examines the role of surrogate endpoints in gene therapy, outlining essential validation criteria, including biological plausibility, analytical reproducibility, and clinical predictive value. Regulatory

Постройте мышцы и защитите миелина.

Множественный склероз (MS) представляет собой хроническое и изнуряющее аутоиммунное заболевание центральной нервной системы (СНС), при котором иммунная реакция, основанная на CNS, разрушает миелин, что приводит к широкому спектру симптомов, включая онемение и покалывание, проблемы зрения, нарушение подвижности и т.д. Oligodendrocytes — это миелионирующие клетки в CNS, которые образуются из олигодендроголовых потомков (OPC) посредством дифференциации. Однако по целому ряду причин ОЗК не проводят различия с олигодендроцитами в РС, и в результате, стимулирование дифференциации ОЗК с олигодендроци

Waldenström Macroglobulinemia - A State-of-the-Art Review: Part 1: Epidemiology, Pathogenesis, Clinicopathologic Characteristics, Differential Diagnosis, Risk Stratification, and Clinical Problems.

Waldenström macroglobulinemia (WM) is an infrequent variant of lymphoma, classified as a B-cell malignancy identified by the presence of IgM paraprotein, infiltration of clonal, small lymphoplasmacytic B cells in the bone marrow, and the MYD88 L265P mutation, which is observed in over 90% of cases. The direct invasion of the malignant cells into tissues like lymph nodes and spleen, along with the immune response related to IgM, can also lead to various health complications, such as cytopenias, hyperviscosity, peripheral neuropathy, amyloidosis, and Bing-Neel syndrome. Chemoimmunotherapy has hi

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… Monoclonal IgM in a patient with paraproteinemic polyneuropathy binds to gangliosides containing disialosyl groups. Ann Neurol. 1985;18:655. doi: 10.1002/ana.410180605. 141. Willison HJ, O’Leary CP, Veitch J, et al. … Human IgM paraproteins demonstrate shared reactivity between Campylobacter jejuni lipopolysaccharides and human peripheral nerve disialylated gangliosides. J Neuroimmunol. 1997;80:23. doi: 10.1016/S0165-5728(97)00130-6. 144. Nobile-Orazio E, Manfredini E, Carpo M, et al. …

Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies.

A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Clinical applications of biomarkers are found in improved diagnosis, monitoring disease progression, and assessing therapeutic correction. These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease. In addition, rece

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… Interestingly, besides glucosylceramide, the ganglioside GM3 is also elevated in Gaucher plasma samples (Ghauharali-van der Vlugt et al. 2007 ). Increases of GM3 have also been noted in spleens of Gaucher patients. This secondary elevation of GM3 may not be without consequences. … Next to elevations in circulating glucosylceramide and gangliosides such as GM3 in Gaucher patients, striking abnormalities in plasma concentrations of some proteins have been identified. …

Targeting Notch-1 positive acute leukemia cells by novel fucose-bound liposomes carrying daunorubicin.

Complete remission by induction therapy in acute myelogenous leukemia (AML) can be achieved due to improvements in supportive and optimized therapy. However, more than 20% of patients will still need to undergo salvage therapy, and most will have a poor prognosis. Determining the specificity of drugs to leukemia cells is important since this will maximize the dose of chemotherapeutic agents that can be administered to AML patients. In turn, this would be expected to lead to reduced drug toxicity and its increased efficacy. We targeted Notch-1 positive AML cells utilizing fucose-bound liposomes

Advanced Technologies for Large Scale Supply of Marine Drugs.

Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure a reliable and sustainable supply of marine natural products (MNPs) for their translation into commercial drugs and other valuable products. From a structural point of view and with few exceptions, MNPs of pharmaceutical importance derive from the so-called secondary metabolism of marine organisms. When production strategies rely on marine macroorganisms, harvesting or culturing coupled with extraction procedures frequently remain t

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… The application of this methodology has been particularly valuable in the production of natural marine gangliosides, which have attracted considerable attention owing to their complexity and neurotrophic activity [ 127 , 128 ]. … The use of an engineered endoglycoceramidase II (EGCase) from Rhodococcus sp. which has been modified to catalyze the synthesis of glycosphingolipids rather than their degradation facilitated the coupling of oligosaccharides with various sphingosines allowing for the creation of structurally diverse gangliosides …

Targeted therapies in pediatric oncology: A start.

The treatment of cancers was revolutionized by the use of combination "conventional" chemotherapy, first in children, during the 20th century. That foundation of therapy, while having achieved significant advances in survival, has reached its limits. Innovations in targeted therapies are now building upon that foundation to further improve outcomes in pediatric oncology. These targeted agents are designed to narrowly utilize specific biologic processes for greater efficacy and optimally fewer generalized toxicities. I will provide an overview of the current spectrum of targeted therapies avail

Novel insight and perspectives of nanoparticle-mediated gene delivery and immune-modulating therapies for pancreatic cancer.

Current standard-of-care therapies have failed to improve the survival of patients with metastatic pancreatic cancer (PCA). Therefore, exploring novel therapeutic approaches for cancer targeting is of utmost need. During the past few years, many efforts have been made to develop conventional treatment strategies to reduce chemotherapy resistance. However, critical challenges have impeded current cancer management outcomes, and limited clinical responses have been achieved due to unfavorable off-target effects. Advances in nanotechnology-based gene and immune-modulator delivery systems have exc

Унификация модели множественного склероза.

Множественный склероз (MS) представляет собой сложное нейродегенеративное расстройство с неразрешенной причиной, ставшей предметом интенсивных исследований. Для разъяснения курса болезни были предложены различные предлагаемые модели. Первостепенные механизмы, как предполагается, основываются на автоматическом иммунитете, в том числе с помощью вирусного имитации эпитопов, хотя и были описаны трудности с классической моделью автономного иммунитета для MS. Одна предыдущая идея, которая включает в себя рассмотрение вирусной самореактивности, заключается в том, что реактивированный вирус HHV-6A мож

Bispecific Antibody-Based Immune-Cell Engagers and Their Emerging Therapeutic Targets in Cancer Immunotherapy.

Cancer is the second leading cause of death worldwide after cardiovascular diseases. Harnessing the power of immune cells is a promising strategy to improve the antitumor effect of cancer immunotherapy. Recent progress in recombinant DNA technology and antibody engineering has ushered in a new era of bispecific antibody (bsAb)-based immune-cell engagers (ICEs), including T- and natural-killer-cell engagers. Since the first approval of blinatumomab by the United States Food and Drug Administration (US FDA), various bsAb-based ICEs have been developed for the effective treatment of patients with