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Chimeric Antigen Receptor T-Cell Revolution Remodeling Immunity to Conquer Autoimmune Disease.

Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking technology in tumor immunotherapy, has demonstrated unprecedented potential in the field of autoimmune diseases in recent years. This article provides a systematic review of the developmental trajectory and core concepts of CAR-T-cell therapy in autoimmune diseases, emphasizing its conceptual evolution from traditional "killing" strategies to "precision immune remodeling". Leveraging multitarget approaches (e.g., CD19 and B-cell maturation antigen) and chimeric autoantigen receptor technology, it achieves efficient elimination

Genetically predicted immune cells and metabolites mediate the causal relationship between inflammatory factors and rheumatoid arthritis.

This study investigates the causal relationship between inflammatory factors and rheumatoid arthritis (RA) and potential immune cells and metabolites mediator using Mendelian randomization. A bidirectional Mendelian randomization study was conducted using statistics from a genome-wide association study database to explore the causal relationship between inflammatory factors and RA, combined with mediation analysis, to discover potential immune cells and metabolites with mediating effects, and to estimate the proportion of total effects mediated by each immune cell and metabolite. The level of

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,

Cytokine release syndrome and cancer immunotherapies - historical challenges and promising futures.

Cancer is the leading cause of death worldwide. Cancer immunotherapy involves reinvigorating the patient's own immune system to fight against cancer. While novel approaches like Chimeric Antigen Receptor (CAR) T cells, bispecific T cell engagers, and immune checkpoint inhibitors have shown promising efficacy, Cytokine Release Syndrome (CRS) is a serious adverse effect and remains a major concern. CRS is a phenomenon of immune hyperactivation that results in excessive cytokine secretion, and if left unchecked, it may lead to multi-organ failure and death. Here we review the pathophysiology of C

Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases.

There are overwhelming reports on the promotional effect of hypoxia on the malignant behavior of various forms of cancer cells. This has been proposed and tested exhaustively in the light of cancer immunotherapy. However, there could be more interesting functions of a hypoxic cellular micro-environment than malignancy. There is a highly intricate crosstalk between hypoxia inducible factor (HIF), a transcriptional factor produced during hypoxia, and nuclear factor kappa B (NF-κB) which has been well characterized in various immune cell types. This important crosstalk shares common activating an

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… Also, the molecular interaction between HIF-1α and B cells has been connected to immunoglobulin class switching ( 51 ). Moreover, HIF-1α has been shown to regulate the expression of key molecules involved in B cell activation, such as CD40 and CD86 ( 52 ). … Germinal center hypoxia potentiates immunoglobulin class switch recombination . J Immunol (Baltimore Md. 1950) ( 2016 ) 197 ( 10 ): 4014 . doi: 10.4049/jimmunol.1601401 PMC5123804 27798169 52 Hazrati A Soudi S Malekpour K Mahmoudi M Rahimi A Hashemi SM . …

Ход работы сессии 31st Европейский педиатрический конгресс по педиатрии: часть 2.

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Perspectives in Melanoma: meeting report from the Melanoma Bridge (December 1st-3rd, 2022-Naples, Italy).

Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), programmed death ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen-4 (CTLA-4). Combinations of these checkpoint therapies with other agents are now being explored to improve outcomes and enhance benefit-risk profiles of treatment. Alternative inhibitory receptors have been identified that may be targeted for anti-tumor immune therapy, such as lymphocyte-activation gene-3 (LAG-3), as have se

Melflufen: A Peptide-Drug Conjugate for the Treatment of Multiple Myeloma.

Despite the availability of new therapies that have led to improved outcomes for patients with multiple myeloma, most patients will eventually relapse. With triplet and even quadruplet combination therapies becoming standard in the first and second line, many patients will have few treatment options after second-line treatment. Melflufen (melphalan flufenamide) is a first-in-class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. Once inside the tumor cells, melflufen is hydrolyzed by peptidases to release alkylator molecules, wh

Tumor buster - where will the CAR-T cell therapy 'missile' go?

Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME

Henoch-Schönlein Purpura Complicated by Hepatocellular Carcinoma.

Although Henoch-Schönlein purpura (HSP) is known to be accompanied by malignancies, cases with hepatobiliary cancer are extremely rare. A 62-year-old man with palpable purpura rapidly extending to both lower legs was admitted to our hospital. He was undergoing follow-up for cirrhosis caused by chronic hepatitis B virus infection and hepatocellular carcinoma (HCC). He had renal dysfunction with hematuria and proteinuria and abdominal pain. Based on the clinical presentation and skin biopsy findings, he was diagnosed with HSP. The administration of steroids resulted in the rapid improvement of t

CAR-T Cell Therapy: Managing Side Effects and Overcoming Challenges.

Chimeric antigen receptor T (CAR-T) cell therapy is an innovative and promising approach to treat cancer. Clinical trials have demonstrated remarkable results, providing hope for patients who have exhausted more traditional therapies. However, this new therapy is not without challenges, as significant side effects have been associated with it. Cytokine release syndrome (CRS) is a widely recognized and consequential side effect of CAR-T cell therapy. Neurological toxicity is another potential side effect that can cause confusion and seizures in some patients. Hematologic toxicities, such as ane

Mechanisms of Action of the New Antibodies in Use in Multiple Myeloma.

Monoclonal antibodies (mAbs) directed against antigen-specific of multiple myeloma (MM) cells have Fc-dependent immune effector mechanisms, such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), but the choice of the antigen is crucial for the development of effective immuno-therapy in MM. Recently new immunotherapeutic options in MM patients have been developed against different myeloma-related antigens as drug conjugate-antibody, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CA

Cell Therapy as a Way to Increase the Effectiveness of Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a standard method for treating a number of pathologies, primarily blood diseases. Timely restoration of the immune system after HSCT is a critical factor associated with the development of complications such as relapses or secondary tumors and various infections, as well as the graft-versus-host reaction in allogeneic transplantation, which ultimately affects the survival of patients. Introduction into the recipient's body of immune system cells that are incapable of sensitization by recipient antigens during the period of immune reconstitution

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… The absence of CD19 + CD27 + memory B cells, reduced levels of circulating immunoglobulins, impaired immunoglobulin class switching, and loss of complexity in immunoglobulin gene rearrangement patterns make patients undergoing allogeneic HSCT susceptible to encapsulated bacteria like Streptococcus pneumoniae …

Новые границы для лечения множественных склерозов: от целесообразных молекулов до биконкретных антител.

Множественный склероз (MS) — аутоиммунное демиелинирующее заболевание центральной нервной системы. С 1990-х годов был достигнут значительный прогресс в развитии терапевтического ландшафта MS, в результате чего было разработано более 20 различных методов лечения заболеваний (ДМТ). Эта терапия эффективно решает проблемы рецидивов и воспаления, но большинство из них не смогли реально предотвратить прогрессирование заболеваний. В то время как классически понимается как состояние с Т-камерой, наиболее эффективные DMT в замедлении движения также нацелены на клетки B. Новые классы методов лечения MS

Improving Kidney Disease Care: One Giant Leap for Nephrology.

Nephrology is an ever-evolving field of medicine. The importance of such a discipline is related to the high clinical impact of kidney disease. In fact, abnormalities of kidney function and/or structure are common in the general population, reaching an overall prevalence of about 10%. More importantly, the onset of kidney damage is related to a strikingly high risk of cardiovascular events, mortality, and progression to kidney failure which, in turn, compromises quality and duration of life. Attempts to comprehend the pathogenesis and molecular mechanisms involved in kidney disease occurrence

B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis.

B-cell maturation antigen (BCMA), expressed in plasmablasts and plasma cells, could serve as a promising therapeutic target for autoimmune diseases. We reported here chimeric antigen receptor (CAR) T cells targeting BCMA in two patients with highly relapsed and refractory myasthenia gravis (one with AChR-IgG, and one with MuSk-IgG). Both patients exhibited favorable safety profiles and persistent clinical improvements over 18 months. Reconstitution of B-cell lineages with sustained reduced pathogenic autoantibodies might underlie the therapeutic efficacy. To identify the possible mechanisms un

Status and Future Directions of Therapeutics and Prognosis of Cardiac Amyloidosis.

Accumulation of aberrant proteins in the heart causes cardiac amyloidosis, an uncommon and complicated illness. It can be classified into two main types: light chain (AL) and transthyretin (ATTR). The diagnosis of cardiac amyloidosis is challenging due to its non-specific clinical presentation and lack of definitive diagnostic tests. Diagnostic accuracy has increased with the advent of modern imaging methods, including cardiac magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. Depending on the severity of cardiac amyloidosis, a number of treatments may be attempted

Руководящие принципы и рекомендации для anti-CD38-based Терапия в области клинической практики для повторной/отправленной миеломы: от Пантихоокеанской рабочей группы по миеломе.

Anti-CD38 Моноклональные антитела (mAbs), включая Daratumumumab и Isatuximab, стали ключевыми компонентами лечения повторной/редактированной множественной миеломы (RRMMM). Этот экспертный консенсус обеспечивает основанные на фактических данных руководящие указания в отношении их оптимального использования, включая выбор режима, особые соображения в отношении пожилых или слабых пациентов и лечение подгрупп высокого риска. Ключевые темы, которые были рассмотрены, включают в себя выбор anti-CD38-based - режимы, стратификация пациентов в результате слабости и коморбидности, стратегии регулирования

Pathogenic Inflammation and Its Therapeutic Targeting in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE, lupus) is a highly complex and heterogeneous autoimmune disease that most often afflicts women in their child-bearing years. It is characterized by circulating self-reactive antibodies that deposit in tissues, including skin, kidneys, and brain, and the ensuing inflammatory response can lead to irreparable tissue damage. Over many years, clinical trials in SLE have focused on agents that control B- and T-lymphocyte activation, and, with the single exception of an agent known as belimumab which targets the B-cell survival factor BAFF, they have been disappoint

Engineering Next-Generation CAR-T Cells for Better Toxicity Management.

Immunoadoptive therapy with genetically modified T lymphocytes expressing chimeric antigen receptors (CARs) has revolutionized the treatment of patients with hematologic cancers. Although clinical outcomes in B-cell malignancies are impressive, researchers are seeking to enhance the activity, persistence, and also safety of CAR-T cell therapy-notably with a view to mitigating potentially serious or even life-threatening adverse events like on-target/off-tumor toxicity and (in particular) cytokine release syndrome. A variety of safety strategies have been developed by replacing or adding variou