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Автологическая трансплантация фекальной микробиоты в целях улучшения результатов пересадки ячеек стм: результаты технико-экономического обоснования в одном центре.

Пересадка стволовых клеток (HSCT) является лечебным методом лечения рака крови, однако ее эффективность подрывается целым рядом острых и хронических осложнений. В свете растущего объема данных, свидетельствующих о том, что эти осложнения связаны с дизобиотическим кишечным микробиомом, мы намеревались оценить возможность трансплантации фекального микробиота (ФМТ) в ходе острой фазы после HSCT. Следует отметить, что в ходе этого испытания был сделан выбор в пользу ДРМ, подготовленной с использованием собственного стула (автологического стула ДРМ) для снижения риска передачи болезни от стула доно

Болезни Увечье с возрастом в экспериментальной модели множественного склероза: роль иммунозенсии.

Начавшийся множественный склероз (MS) у пожилых людей соотносится с более высоким риском развития первичных прогрессивных MS, ускорения перехода к вторичным прогрессивным MS и увеличения накопления инвалидности. Это явление может быть связано с возрастными изменениями в иммунной системе: с возрастом иммунная система проходит процесс, называемый иммунной сенсацией, который характеризуется снижением функции как врожденной, так и адаптивной иммунной реакции. Такое снижение может привести к снижению способности контролировать воспаление и восстанавливать поврежденные ткани. Кроме того, пожилые люд

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… LAG‐3, lymphocyte activating gene 3; MHC, major histocompatibility complex; PD‐1, programmed cell death protein 1; Tcm, central memory T; Te, effector T; Tem, effector memory T; Th, helper T; TIM‐3, T cell immunoglobulin and mucin domain‐containing protein‐3; Tn, naïve T; Treg, regulatory T. … Moreover, B cells from aged mice already presented increased expression of major histocompatibility complex (MHC)‐II in the basal condition (non‐immunized aged mice), and were found increased respect to young counterparts in the inflammatory phase of EAE (Figure  5I ) and followed a different evolution …

Evaluating the Therapeutic Potential of Idecabtagene Vicleucel in the Treatment of Multiple Myeloma: Evidence to Date.

Over the past two decades, significant progress has been made in the diagnosis, risk assessment and treatment of patients with multiple myeloma, translating into remarkable improvements in survival outcomes. Yet, cure remains elusive, and almost all patients eventually experience relapse, particularly those with high-risk and refractory disease. Immune-based approaches have emerged as highly effective therapeutic options that have heralded a new era in the treatment of multiple myeloma. Idecabtagene vicleucel (ide-cel) is one such therapy that employs the use of genetically modified autologous

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… CAR Design and Overview of Therapy Deconstructing the Ide-Cel Construct T-cell activation by T-cell receptors (TCRs) is a multistep process that is crucially dependent upon antigen presentation by major histocompatibility complex (MHC) proteins as well as subsequent signaling through costimulatory … Major Histocompatibility Complex (MHC) class I and MHC class II proteins: conformational plasticity in antigen presentation. Front Immunol . 2017;8. doi: 10.3389/fimmu.2017.00292 45. Hwang J-R, Byeon Y, Kim D, Park S-G. …

Tailoring cells for clinical needs: Meeting report from the Advanced Therapy in Healthcare symposium (October 28-29 2017, Doha, Qatar).

New technologies and therapies designed to facilitate development of personalized treatments are rapidly emerging in the field of biomedicine. Strikingly, the goal of personalized medicine refined the concept of therapy by developing cell-based therapies, the so-called "living drugs". Breakthrough advancements were achieved in this regard in the fields of gene therapy, cell therapy, tissue-engineered products and advanced therapeutic techniques. The Advanced Therapies in Healthcare symposium, organized by the Clinical Research Center Department of Sidra Medicine, in Doha, Qatar (October 2017),

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… MSCs are non-hematopoietic cells expressing different surface molecules (including CD90, CD73, CD105, CD29, CD44, and CD166), but lacking the expression of endothelial or hematopoietic markers (CD31, CD45, CD43, CD14, CD11b), major histocompatibility complex (MHC) class II molecule, and costimulatory … histocompatibility complex mesenchymal stromal cells natural killer overall survival Perianal Disease Activity Index post-transplant lymphoproliferative disorder type 1 diabetes type 2 diabetes tumor microenvironment Contributor Information Sara Deola, Email: sdeola@sidra.org. …

Twenty-five years of type I interferon-based treatment: a critical analysis of its therapeutic use.

The clinical exploitation of type I interferon (IFN) as an antiviral and antineoplastic agent is based on the properties originally attributed to this cytokine family, with schedules reflecting only their antiviral and antiproliferative activities. Nevertheless, type I IFN has emerged as a central activator of the innate immunity. As current schedules of treatment for chronic hepatitis C and for hematological and solid tumors, based on the continuous administration of recombinant type I IFN or pegylated formulations, disregard viral resistance, host genetic variants predicting treatment outcom

CAR-T Therapy Can Be a Useful Treatment Modality for More Than Just Hematologic Malignancies.

Chimeric antigen receptor-T-cell (CAR-T) therapy for hematologic malignancies has made significant advancements over the years, and it is now incorporated as a treatment algorithm. Early phase clinical trials are underway for various solid tumors, and the effectiveness of CAR-T cell therapy has been demonstrated for specific types of glioma and several solid tumors. However, its efficacy does not match that observed in hematological malignancies. Recently, a case series reported CAR-T cell therapy targeting CD19 for autoimmune diseases such as systemic lupus erythematosus, leading to a dramati

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… The T-cell receptor (TCR) recognizes complexes of antigen peptides and the self-major histocompatibility complex (MHC), and it plays a crucial role in highly personalized biological defense, thus making it challenging to develop universal “off-the-shelf” therapies. Currently, the U.S. …

Glatiramer Acetate модифицирует иммунные портреты моноцито-супружеских клеток in Vitro без последствий для их поколения.

Глатирамер ацетат (GA) является первой строевой терапией для повторного выброса множественных склерозов (MS) и все чаще демонстрирует многообещающие терапевтические выгоды в ряде других условий. Несмотря на его широкое применение, точный фармакологический механизм ГА остается неясным. Помимо клеток T и B, дендритные клетки (DC) и моноциты играют важную роль в нейроинфламации, связанной с MS, позиционируя их в качестве потенциальных первоначальных целей для GA. Здесь мы изучили влияние GA на дифференциацию моноцитов человека от здоровых доноров к моноцитным дендритным клеткам (MODC) и оценили и

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… Our data clearly demonstrate that in vitro exposure of moDCs to GA results in a significant increase in the expression of activation and co-stimulatory markers, including CD83, CD86, and major histocompatibility complex (MHC) class II molecules (HLA-DR), indicating that these cells may actively engage …

Сфингосин-1-Фосфатная модуляция в неврологических расстройствах: Отчёты от MS и Stroke.

Множественный склероз — это хроническое аутоиммунное заболевание, при котором иммунная система атакует защитную оболочку или миелин, покрывающую нервные волокна, что влияет на способность мозга общаться с другими частями тела. Эта аномальная иммунная реакция привлекает подстрекательские вещества, которые выглядят как повреждения мозга и спинного мозга. Инсульт характеризуется внезапным ухудшением неврологической функции в результате потери или ограничения кровотока в результате острого повреждения локального участка центральной нервной системы, включая мозг, сетчатку или спинной мозг. В то вре

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… Through the binding of major histocompatibility complexes, the drug can effectively target all immune antigen-presenting cells [ 13 ]. Recent studies have shown the promising effects of a chemical drug known as fingolimod (Gilenya TM ). …

The B-cell-autoantibody axis in lung cancer immunity.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality, and while immune checkpoint inhibitor (ICI) has transformed treatment, resistance remains a critical challenge. Beyond the T-cell-centric view, tumor-infiltrating B lymphocytes (TIL-Bs) and tertiary lymphoid structures (TLSs) have emerged as pivotal prognostic determinants; however, the mechanistic interplay within the B-cell-autoantibody axis remains underexplored. Unlike previous reviews that primarily catalogue B-cell abundance, this synthesis integrates emerging evidence from single-cell RNA sequencing

Impact of Hyperglycemia and Diabetes Mellitus on Breakthrough Mucormycosis Outcomes in Patients with Hematologic Malignancies-Complex and Intriguing Associations.

Mucormycosis (MCR) is frequently associated with diabetic ketoacidosis and hyperglycemia, as well as hematologic malignancies (HMs) and hematopoietic stem cell transplantation (HSCT). However, little is known about the effect of hyperglycemia on MCR outcomes in patients with HMs. We therefore conducted a retrospective cohort study of adult patients hospitalized with MCR and HM or HSCT (n = 103) at MD Anderson Cancer Center from April 2000 through to April 2020. Twenty-three patients (22%) had documented episodes of severe hyperglycemia. Sixty patients had >5 serum glucose measurements within 2

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… Furthermore, insulin receptor signaling can enhance the expression of major histocompatibility complex molecules that are required for optimal antigen presentation to T cells, polarize host immunity toward an adaptive lymphoid cell-driven response, and boost T-cell immunity through nutrient uptake and …

Transplantation Tolerance through Hematopoietic Chimerism: Progress and Challenges for Clinical Translation.

The perception that transplantation of hematopoietic stem cells can confer tolerance to any tissue or organ from the same donor is widely accepted but it has not yet become a treatment option in clinical routine. The reasons for this are multifaceted but can generally be classified into safety and efficacy concerns that also became evident from the results of the first clinical pilot trials. In comparison to standard immunosuppressive therapies, the infection risk associated with the cytotoxic pre-conditioning necessary to allow allogeneic bone marrow engraftment and the risk of developing gra

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… Nevertheless, the conditioning was sufficient to achieve tolerance to renal allografts across major histocompatibility complex (MHC) barriers as long as the kidney was transplanted before the loss of peripheral chimerism ( 44 ). … Abbreviations ATG, α-thymocyte globulin; HLA, human leukocyte antigen; MHC, major histocompatibility complex; NK, natural killer; NKT, natural killer T cells; TLI, total lymphoid irradiaton; TBI, total body irradiation; Treg, regulatory T cells. References 1. Grinyo JM. …

Understanding the Mechanisms of Resistance to CAR T-Cell Therapy in Malignancies.

Taking advantage of the immune system to exert an antitumor effect is currently a novel approach in cancer therapy. Adoptive transfer of T cells engineered to express chimeric antigen receptors (CARs) targeting a desired antigen has shown extraordinary antitumor activity, especially in refractory and relapsed B-cell malignancies. The most representative in this respect, as well as the most successful example, is CD19 CAR T-cell therapy in B-cell acute lymphoblastic leukemia (B-ALL). However, with the widespread use of CAR T-cell therapy, problems of resistance and relapse are starting to be co

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… CAR T cells, a type of genetically engineered peripheral T cell, have a special antigen receptor whose extracellular single-chain variable fragment (scFv) can directly recognize a specific antigen independent of the major histocompatibility complex (MHC), an intracellular CD3ζ domain that conveys the … Food and Drug Administration granulocyte-colony stimulating factor hematopoietic stem cell transplantation Interleukin 6 immunogenic cell death interferon janus kinase Lymphocyte-activation gene 3 major histocompatibility complex multiple myeloma messenger RNA Histone-lysine N-methyltransferase …

The potential value of cancer-testis antigens in ovarian cancer: Prognostic markers and targets for immunotherapy.

BackgroundTumor immunotherapy has become an important adjuvant therapy after surgery, radiotherapy, and chemotherapy. In recent years, the role of tumor-associated antigen (TAA) in tumor immunotherapy has become increasingly prominent. Cancer-testis antigen (CTA) is a kind of TAA that is highly restricted in a variety of tumors and can induce an immune response.AimsThis review article aimed to evaluate the role of CTA on the progression of ovarian cancer, its diagnostic efficacy, and the potential for immunotherapy.MethodsWe analyzed publications and outlined a comprehensive of overview the re

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… Treatment of patients with metastatic cancer using a major histocompatibility complex class II‐restricted T‐cell receptor targeting the cancer germline antigen MAGE‐A3 . … Treatment of ovarian cancer cell lines with 5‐aza‐2′‐deoxycytidine upregulates the expression of cancer‐testis antigens and class I major histocompatibility complex‐encoded molecules . …

Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities.

New-generation vaccines, formulated with subunits or nucleic acids, are less immunogenic than classical vaccines formulated with live-attenuated or inactivated pathogens. This difference has led to an intensified search for additional potent vaccine adjuvants that meet safety and efficacy criteria and confer long-term protection. This review provides an overview of protein-based adjuvants (PBAs) obtained from different organisms, including bacteria, mollusks, plants, and humans. Notably, despite structural differences, all PBAs show significant immunostimulatory properties, eliciting B-cell- a

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… Subsequently, protein antigens in the form of peptide fragments are carried to the surface of APCs on Major Histocompatibility Complex class I (MHC-I) and class II (MHC-II) proteins, stimulating antigen-specific T-cell responses, and thus develop the cellular-mediated adaptive immunity, which involves … Porins from Fusobacterium nucleatum (FomA), a human oral pathogen [ 36 ], induces IL-6 secretion and cell surface upregulation of CD86 and major histocompatibility complex (MHC) type II in splenic B cells. …

The Impact of NLRP3 Activation on Hematopoietic Stem Cell Transplantation.

NLR family pyrin domain-containing 3 (NLRP3) is an intracellular protein that after recognizing a broad spectrum of stressors, such as microbial motifs and endogenous danger signals, promotes the activation and release of the pro-inflammatory cytokines IL-1β and IL-18, thus playing an essential role in the innate immune response. Several blood cell types, including macrophages, dendritic cells, and hematopoietic stem and progenitor cells (HSPCs), express NLRP3, where it has been implicated in various physiological and pathological processes. For example, NLRP3 participates in the development a

Multiple Myeloma: A Review of the Literature and a Case Report Highlighting the Immunocompromised State of Myeloma Patients.

Multiple myeloma (MM), a malignancy involving plasma cells, disproportionately affects older adults with an average age of diagnosis of about 70 years. Oftentimes, the therapies used in the treatment of MM are associated with a risk for immunotoxicity, lowering the ability of the immune system to fight off opportunistic infections. This is an important relationship for clinicians to realize as the incidence of opportunistic infections in myeloma patients is increasing. As an example, we present a case of a patient with MM who subsequently developed a cryptococcal infection. Our paper will high

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… CAR-T cells are genetically engineered T cells, composed of T-cell receptors with extracellular receptors specially designed to target tumor-specific antigens as well as transmembrane and intracellular domains that render co-stimulatory signaling and major histocompatibility complex (MHC) binding unnecessary …

Библиометрический анализ исследований в области контроля за конкретными случаями, касающихся связи между аллеями АВП и множественным склерозом у взрослых.

Множественный склероз (MS) представляет собой сложное аутоиммунное заболевание, которое влияет на центральную нервную систему (CNS), при этом генетические и экологические факторы играют важную роль в ее развитии и развитии. Одним из наиболее важных генетических факторов, связанных с MS, является генный комплекс HLA. Взаимосвязь между ВУЗом и МЗ стала предметом многочисленных исследований, однако до настоящего времени не сообщалось о результатах библиометрического анализа этих исследований. Поэтому цель этого исследования состояла в том, чтобы дать всеобъемлющий обзор выпуска публикаций, влияни

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… The paper with the highest citation count is “A Complete Genomic Screen for Multiple Sclerosis Underscores a Role for the Major Histocompatibility Complex” by Haines J.L. et al., published in 1996, with 813 citations. …

Polypharmacology: new drugs in 2023-2024.

Polypharmacology is an emerging approach to drug design and development that involves the use of multi-target-directed ligands (MTDLs), agents capable of interacting with multiple biological targets simultaneously. The effective treatment of chronic and multifactorial conditions, driven by the dysregulation of multiple interconnected pathways, such as cancer, autoimmune and metabolic disorders, cardiovascular and neurodegenerative diseases, is one of the most substantial challenges in contemporary pharmacology. 'Traditional' single-target-based treatment frequently shows limited effectiveness,

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… Noteworthy, this effect occurs regardless of native T-cell receptor specificity and does not involve major histocompatibility complex (MHC) class 1 molecules [ 44 – 45 ]. Each agent shows a relatively high response rate in monotherapy in patients with heavily pretreated MM [ 46 ]. … histocompatibility complex Machine learning Multiple myeloma Multi-target-directed ligand(s) Mammalian target of rapamycin serine/threonine protein kinase Nuclear factor kappa-light-chain-enhancer of activated B cells Primary biliary cholangitis Pyrrolobenzodiazepine Programmed cell death protein …

CART-Cell Therapy: Recent Advances and New Evidence in Multiple Myeloma.

Despite the improvement in survival outcomes, multiple myeloma (MM) remains an incurable disease. Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) represents a new strategy for the treatment of relapsed/refractory MM (R/R). In this paper, we describe several recent advances in the field of anti-BCMA CAR T-cell therapy and MM. Currently, available data on anti-BCMA CART-cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated R/R MM patients. Despite this, the main issues remain to be addressed. First of all, a significant pro

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… Several novel bioengineering methods (i.e., knocking out the T-cell receptor and major histocompatibility complex expression using various gene-editing techniques) have been implemented to moderate potential graft-versus-host toxicity and host rejection. … MHC I: To improve CART-cell persistence and increase the chance for durable remissions, we could use CRISPR/Cas9 to eliminate the class I major histocompatibility complex (MHC I) expressed on the surface of our CAR T product candidates. …

Ten tips for an onco-nephrology clinic.

An increasing number of cancer patients are benefiting from long term cancer-directed therapy with an ever-expanding arsenal of novel agents from monoclonal antibodies to small molecules and cellular therapies in addition to the mainstay cytotoxic chemotherapy. All these therapies are accompanied by a unique array of adverse events, which include kidney toxicity. In this context, the need for onco-nephrology expertise continues to grow. Oncologists and hematologists collaborate closely with onco-nephrologists to determine: (i) treatment options for special populations based on accurate assessm