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Предлагаемый протокол наблюдений для ранней дифференциации синдрома высвобождения цитокина и сепсиса в реципиентах CAR-T с гематологическими аномалиями с использованием IL-6Соотношение ПХТ: исследование ДРАКАРИС.

Терапия антигенного рецептора T-клеток (CAR-T) произвела революцию в лечении гематологических магнатов, продемонстрировав замечательную эффективность в лейкемиях B-клеток, лимфомах и множестве миелом. Однако синдром сильного токсина, особенно синдрома цитокина (CRS) и сепсиса, сопряженный с серьезными клиническими проблемами. Оба эти условия имеют совпадающие черты, включая лихорадку, гипотенцию и многоорганическую дисфункцию, что делает важную роль своевременной и точной дифференциации. В основе ДУС лежит чрезмерное высвобождение цитокина, главным образом IL-6, и лечится IL-6 Блокада рецептор

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… CARs are engineered synthetic receptors designed to redirect lymphocytes, primarily T cells, to identify and eliminate target antigen-expressing cells, independent of Major Histocompatibility Complex (MHC) presentation. …

An Overview of the Strategies to Boost SARS-CoV-2-Specific Immunity in People with Inborn Errors of Immunity.

The SARS-CoV-2 pandemic has heightened concerns about immunological protection, especially for individuals with inborn errors of immunity (IEI). While COVID-19 vaccines elicit strong immune responses in healthy individuals, their effectiveness in IEI patients remains unclear, particularly against new viral variants and vaccine formulations. This uncertainty has led to anxiety, prolonged self-isolation, and repeated vaccinations with uncertain benefits among IEI patients. Despite some level of immune response from vaccination, the definition of protective immunity in IEI individuals is still un

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… AIMS, activation-induced markers; DNBSEQ, DNA nanoballs sequencing; EliA, Enzyme fluoroimmunoassay; ELISA, enzyme-linked immunosorbent assay; ELISPOT, enzyme-linked immunosorbent spot; IgG, Immunoglobulin G; IGRA, IFN-γ release assay; pMHCI, peptide major histocompatibility complex I; pMHCII, peptide … major histocompatibility complex II; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus-2. …

Emerging role of carfilzomib in treatment of relapsed and refractory lymphoid neoplasms and multiple myeloma.

Proteasome inhibition forms the cornerstone of antimyeloma therapy. The first-in-class proteasome inhibitor, bortezomib, either alone or in combination with other chemotherapeutic agents, induces high overall response rates and response qualities in patients with clinically and molecularly defined high-risk disease. However, resistance to bortezomib and neurotoxicity associated with the treatment remain challenging issues. Carfilzomib is a novel, well tolerated, irreversible proteasome inhibitor with minimal neurotoxicity. Carfilzomib demonstrates promising activity in myeloma patients who are

DOK2 Has Prognostic and Immunologic Significance in Adults With Acute Myeloid Leukemia: A Novel Immune-Related Therapeutic Target.

BackgroundThe role of downstream tyrosine kinase 2 (DOK2), a major member of the DOK family, remains poorly defined in acute myeloid leukemia (AML). Herein, we investigated the expression levels, clinical outcomes, and biological functions of DOK2 in patients with AML.MethodsDatasets were obtained from the Cancer Genome Atlas (TCGA) database for transcriptomic and clinical information. Nomogram construction and assessment were conducted using Cox regression analysis, receiver operating characteristic (ROC) curves, and calibration plots. Public databases, including the Gene Expression Omnibus,

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… The correlations of DOK2 with the expressions of chemokines, chemokine receptors, and immunomodulators comprising immune-inhibitors, immune-stimulators, and major histocompatibility complex (MHC) molecules are shown in heat maps ( Supplementary Figures S5C–G ). …

Endothelial cell function and endothelial-related disorders following haematopoietic cell transplantation.

Use of haematopoietic cell transplantation (HCT) in the treatment of haematologic and neoplastic diseases may lead to life-threatening complications that cause substantial morbidity and mortality if untreated. In addition to patient- and disease-related factors, toxicity associated with HCT puts patients at risk for complications that share a similar pathophysiology involving endothelial cells (ECs). Normally, the endothelium plays a role in maintaining homeostasis, including regulation of coagulation, vascular tone, permeability and inflammatory processes. When activated, ECs acquire cellular

Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma.

The proteasome is crucial for the degradation of intracellular proteins and plays an important role in mediating a number of cell survival and progression events by controlling the levels of key regulatory proteins such as cyclins and caspases in both normal and tumor cells. However, compared to normal cells, cancer cells are more dependent on the ubiquitin proteasome pathway (UPP) due to the accumulation of proteins in response to uncontrolled gene transcription, allowing proteasome to become a potent therapeutic target for human cancers such as multiple myeloma (MM). Up to date, three protea

Nanomaterials in gene therapy and genome editing: challenges and emerging directions.

Nanomaterials are redefining the landscape of gene and genome editing, yet their translation to clinical reality remains constrained by multiple unresolved challenges. While they provide structural and functional advantages for delivering nucleic acids and CRISPR/Cas systems across biological barriers, their behavior within living systems is often unpredictable, leading to issues such as off-target editing, immune activation, and inconsistent biodistribution. The design of nanocarriers, whether lipid-based, polymeric, inorganic, must therefore balance efficiency with safety, integrating physic

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… This response is driven by enhanced antigen presentation via major histocompatibility complexes (MHC), the engagement of co-stimulatory receptors, and secretion of pro-inflammatory cytokines. The lower part illustrates antigen delivery alongside poly(lactic-co-glycolic acid) (PLGA) nanoparticles. … The figure highlights key molecules such as IFN-γ (interferon-γ), IL (interleukin), MHC (major histocompatibility complex), TCR (T-cell receptor), and TNF (tumor necrosis factor).Reprinted from [ 365 – 369 ] with permission from Springer Nature Clinical development of nanoparticles for gene delivery …

Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma.

The gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This review provides a comprehensive overview of current insights into the influence of the gut microbiota on HCC progre

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… CD8+T cells play a pivotal role in the anti-tumor response by recognizing the major histocompatibility complex polypeptide complex expressed on cancer cells via their T cell receptors. CD4+T cells can be classified into two distinct subsets, namely Th1 and Th2 subsets ( 45 ). …

Current State of the Art and Prospects of T Cell-Redirecting Bispecific Antibodies in Multiple Myeloma.

Multiple myeloma (MM) patients eventually develop multi-drug-resistant disease with poor survival. Hence, the development of novel treatment strategies is of great importance. Recently, different classes of immunotherapeutic agents have shown great promise in heavily pre-treated MM, including T cell-redirecting bispecific antibodies (BsAbs). These BsAbs simultaneously interact with CD3 on effector T cells and a tumor-associated antigen on MM cells, resulting in redirection of T cells to MM cells. This leads to the formation of an immunologic synapse, the release of granzymes/perforins, and sub

The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.

The cytokine network is the central regulatory system for intercellular communication within the immune system. Its proper function depends on the dynamic balance between pro-inflammatory and anti-inflammatory cytokines. Through complex positive and negative feedback loops, this balance precisely regulates the intensity and duration of immune responses, thereby playing a critical role in both physiological and pathological states. This review systematically summarizes the compositional features and classification framework of the cytokine network, as well as the mechanisms by which it maintain

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… TGF-β1 exerts potent immunosuppressive effects by downregulating the expression of major histocompatibility complex (MHC) class II molecules on dendritic cells and T cells and by inhibiting immune cell proliferation and activation [ 38 ]. …

Immunotherapeutic approaches for systemic lupus erythematosus: early overview and future potential.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Current SLE therapies include immunosuppressants, antimalarial drugs, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroids, but these treatments can cause substantial toxicities to organs and may not be effective for all patients. In recent years, significant progress has been made in the treatment of SLE using immunotherapy, including Benlysta and Saphnelo. These advances in immunotherapy hold promise for SLE patients, providing new therapeutic options that may offer better clinical benefit and effectiveness. S

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… Treatment with rigerimod caused inhibition of T cell activation, reduced expression of major histocompatibility complex class II (MHC II) in antigen-presenting cells (APCs), and decrease in proteinuria and anti-dsDNA antibody in lupus-prone mouse model [ 84 , 85 ]. …

Impact of Glucocorticoid Use in Oncology in the Immunotherapy Era.

Thanks to their anti-inflammatory, anti-oedema, and anti-allergy properties, glucocorticoids are among the most widely prescribed drugs in patients with cancer. The indications for glucocorticoid use are very wide and varied in the context of cancer and include the symptomatic management of cancer-related symptoms (compression, pain, oedema, altered general state) but also prevention or treatment of common side effects of anti-cancer therapies (nausea, allergies, etc.) or immune-related adverse events (irAE). In this review, we first give an overview of the different clinical situations where

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… Antigen-presenting cells (APC) present antigens as peptides bound to major histocompatibility complex (MHC) class I or class II molecules to active CD8+ or CD4+ T-lymphocytes, respectively. …

Одиссей моноколональных гаммопатий: сосредоточен на прекурсорах и переходе от MGUS и SMM к нескольким Myeloma, с кратким обзором новых терапевтических стратегий.

Моноклональные гаммопатии охватывают континуум от моноклональной гаммопатии неопределенного значения (MMUS) и заморозки нескольких миелом (SMM) до открытой множественной миеломы (MM). Эта постепенная клональная эволюция обусловлена первичными цитогенетическими повреждениями, вторичными геномными явлениями и эпигенетической реконструкцией в допустимой микроокружающей среде костного мозга. Традиционные биомаркеры (коэффициенты сыворотки М-протеина и свободных световых цепей) обеспечивают полезную, но неполную прогнозную информацию, поскольку они не отражают пространственной неоднородности или вр

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… This design promotes robust T-cell activation, proliferation, and cytotoxicity, independent of major histocompatibility complex (MHC) presentation, enabling precise and potent tumor cell killing [ 198 ]. …

Association of Epistatic Effects of lncRNA GAS5, miR-146a, IRAK-1, and miR-155 Genetic Variants with Multiple Sclerosis Risk and Severity.

The complex genetic architecture of heritability in multiple sclerosis (MS) remains undisclosed mainly. Epistasis (gene-gene interaction) substantially impacts MS; however, it is largely unexplored, especially among the non-coding RNA genes and their targets. The long non-coding RNA GAS5 exacerbates demyelination and sponges miR-146a and miR-155, impeccable contributors to MS pathogenesis. miR-146a negatively regulates the immune responses by targeting IRAK-1. We investigated the association of epistatic effects and haplotypes of five single nucleotide polymorphisms (SNPs), GAS5 rs2067079, miR

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… These GWAS have identified 32 major histocompatibility complex (MHC) variants and over 200 non-MHC candidate variants associated with MS, with the haplotype HLA-DRB1*15:01 (MHC, chromosome 6p21.3) having the most substantial impact [ 10 , 12 ]. …

Low-dose anti-thymocyte globulin plus low-dose post-transplant cyclophosphamide-based regimen for prevention of graft-versus-host disease after haploidentical peripheral blood stem cell transplants: a large sample, long-term follow-up retrospective study.

INTRODUCTION: The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity for prevention of graft-versus-host disease (GVHD) in haploidentical-peripheral blood stem cell transplantation (haplo-PBSCT), but its impacts on long-term outcomes remain to be defined. METHODS: We performed a large sample, long-term follow-up retrospective study to evaluate its efficacy for GVHD prophylaxis. RESULTS: The study enrolled 260 patients, including 162 with myeloid malignancies and 98 with lymphoid

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… Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide. Blood (2001) 98(12):3456–64. doi: 10.1182/blood.v98.12.3456 9. …

Extracellular Vesicles After Allogeneic Hematopoietic Cell Transplantation: Emerging Role in Post-Transplant Complications.

Extracellular vesicles (EVs) play an important role in the cellular crosstalk by transferring bioactive molecules through biological barriers from a cell to another, thus influencing recipient cell functions and phenotype. Therefore, EVs are increasingly being explored as biomarkers of disease progression or response to therapy and as potential therapeutic agents in different contexts including in hematological malignancies. Recently, an EV role has emerged in allogeneic hematopoietic cell transplantation (allo-HCT) as well. Allogeneic hematopoietic cell transplantation often represents the on

CAR-T cells in the treatment of multiple myeloma: an encouraging cell therapy.

Multiple myeloma (MM) is a malignant disease of plasma cells that accounts for approximately 10% of all hematological malignancies and is characterized by a clonal proliferation of malignant plasma cells in the bone marrow. Numerous therapeutic strategies, including proteasome inhibitors, immunomodulators, monoclonal antibodies against CD38 and autologous stem cell transplantation, have prolonged the median survival of MM patients. Nevertheless, almost all MM patients suffer disease relapses due to drug resistance and eventually die from MM or MM-related complications. Chimeric antigen recepto

Redox Remodeling by Nutraceuticals for Prevention and Treatment of Acute and Chronic Inflammation.

Antioxidant-rich dietary regimens are considered the best practice to maintain health, control inflammation, and prevent inflammatory diseases. Yet, nutraceuticals as food supplements are self-prescribed and purchasable over the counter by healthy individuals for the purpose of beneficial effects on fitness and aging. Hence, the effectiveness, safety, and correct intake of these compounds need to be better explored. Since redox-modulating activity of these compounds appears to be involved in activation and or suppression of immune cells, the preventive use of nutraceuticals is very attractive

Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence.

Conventional immunotherapy has emerged as a key option for cancer treatment. However, its efficacy has been limited in urological cancers, especially prostate cancer, because of the immunosuppressive tumor microenvironment (TME), difficulty in drug delivery, aberrant immune response, and damage to normal cells. Bispecific antibodies (BsAbs) are engineered proteins with two different antigen-binding domains, designed using different technologies and in various formats. BsAb-based tumor immunotherapy has yielded optimistic results in preclinical and clinical investigations of many tumor types, i

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… Owing to the fact that BsAbs mostly activate T cells through binding of the ε subunit of CD3 in the TCR complex, they bypass the major histocompatibility complex (MHC) restriction and induce activation without antigen presentation 75 . … histocompatibility complex magnetic resonance imaging maximum tolerated dose non-muscle invasive bladder cancer non-small cell lung cancer objective response rate overall survival programmed cell death 1 programmed cell death 1 ligand 1 prostate health index prostate-specific Ag prostate-specific …

CAR-NK cell therapy for hematological malignancies.

AbstractChimeric antigen receptor (CAR)-natural killer (NK) cells represent a novel cell therapy platform distinguished from CAR T cells by their more favorable safety profile, easier off-the-shelf allogeneic manufacturing and consequent scalability, and their innate cytotoxicity without needing previous sensitization. CAR-NK cells derived from a variety of sources have been used against hematologic malignancies in several clinical trials, showing significant therapeutic responses and efficacy without severe adverse effects. Limitations that are being addressed in CAR-NK cell therapy include c