Результаты поиска

CAR T cells: engineered immune cells to treat brain cancers and beyond.

Malignant brain tumors rank among the most challenging type of malignancies to manage. The current treatment protocol commonly entails surgery followed by radiotherapy and/or chemotherapy, however, the median patient survival rate is poor. Recent developments in immunotherapy for a variety of tumor types spark optimism that immunological strategies may help patients with brain cancer. Chimeric antigen receptor (CAR) T cells exploit the tumor-targeting specificity of antibodies or receptor ligands to direct the cytolytic capacity of T cells. Several molecules have been discovered as potential t

Совпадение в полном тексте источника
… When used to treat tumors with minimal tumor mutational burden, such as the majority of brain tumors, CARs can target tumors without altering how the major histocompatibility complex (MHC) expresses its antigens [ 4 , 5 ]. … Abbreviations Chimeric antigen receptor T cells Central nervous system Chimeric antigen receptors Major histocompatibility complex Blood-brain barrier Blood-brain tumor barrier T cell receptor T cell receptor α constant Food and drug administration Authors’ contributions Conceptualization, …

Uncovering the knowledge about systemic amyloidosis relevant to the rheumatologists.

Amyloidosis is a localized or systemic disease caused by deposition of proteins in the extracellular space of various organs and tissues. As part of the disease, proteins that were originally soluble misfold and acquire a fibrillar conformation that renders them insoluble and resistant to proteolysis. Systemic amyloidosis is a rare, often underdiagnosed condition. In recent years, the incidence of newly diagnosed cases of amyloidosis has been increasing in association with the aging of the population and greater access to diagnostic tests. From a clinical perspective, systemic amyloidosis is f

B-cell targeted therapeutics in clinical development.

B lymphocytes are the source of humoral immunity and are thus a critical component of the adaptive immune system. However, B cells can also be pathogenic and the origin of disease. Deregulated B-cell function has been implicated in several autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. B cells contribute to pathological immune responses through the secretion of cytokines, costimulation of T cells, antigen presentation, and the production of autoantibodies. DNA-and RNA-containing immune complexes can also induce the production of type

Совпадение в полном тексте источника
… histocompatibility complex; MS: multiple sclerosis; NF: nuclear factor; PC: plasma cell; PML: progressive multifocal leukoencephalopathy; RA: rheumatoid arthritis; RRMS: relapsing remitting multiple sclerosis; SLE: systemic lupus erythematosus; TEARS: Tolerance and Efficacy of Rituximab in Sjogren's … Antigen-unspecific B cells and lymphoid dendritic cells both show extensive surface expression of processed antigen-major histocompatibility complex class II complexes after soluble protein exposure in vivo or in vitro. J Exp Med. 1997;186:673–682. doi: 10.1084/jem.186.5.673. …

Эффективность и безопасность иммуноадсорбции как спасательной терапии подстрекательских миопатий: доклад three - обзор дел и литературы.

Идиопатическая воспалительная миопатия (МИМ) резюмирует редкие, системные аутоиммунные условия, характеризующиеся главным образом провокационным повреждением скелетной мышцы. Несмотря на то, что мышечные мышцы повреждены в первую очередь, эти заболевания, связанные с IIM, связаны с другими органами, включая кожу, легкие, верхний желудочно-кишечный тракт, суставы и сердце. Несмотря на то, что многие пациенты адекватно реагируют на иммунодепрессивное лечение, некоторые пациенты развивают быстро прогрессивные и устойчивые к лечению жизнестойкие курсы. Для лечащего врача ИИМ является сложным делом

Совпадение в полном тексте источника
… Histopathological evaluation of her muscle biopsy (performed in the referring center) presented necrotizing muscular atrophy and upregulation of major histocompatibility complex (MHC) class I molecules on muscle fibers. …

BATF2 является регулятором интерферона β, сигнализирующего в астроцитах во время нейроинфламмации.

Астроцитический интерферон (IFN) (IFN) (информация) связан с уменьшением нейроинфламмации; однако эффекторы вниз по течению, ответственные за регулирование этой защиты, неизвестны. Здесь мы идентифицируем удельный коэффициент транскрипции IFN, основной коэффициент транскрипции лейцина АТФ-подобный АТФ2, который играет ключевую роль в модулировании последствий ITFN, сигнализирующих в астроцитах. Последовательность иммунопреобразования Хроматина показала, что НИМФ2 связывает и предотвращает перевыражение регулятивных факторов IFN (IRF)1 и IRF1, таких как caspase-1. Мы также показываем, что мыши

Совпадение в полном тексте источника
… HLA-DMB , HLA-DQB1 , and HLA-DOA transcribe proteins involved in major histocompatibility complex (MHC) class II antigen presentation, 27 while INHBE transcribes the preproprotein inhibin subunit βE, which is primarily expressed in the pancreas and liver and is a member of the transforming growth …

Bispecific antibodies in the treatment of epithelial ovarian, endometrial, and cervical cancer: an overview of current applications, challenges, and emerging opportunities.

Gynecological cancer remains one of the leading causes of mortality worldwide. Recent advances in genomic and molecular sequencing have significantly enhanced our understanding of the biological pathways that drive tumor progression and resistance to therapy. Targeted therapies, including monoclonal antibodies (mAbs), have revolutionized cancer treatment by selectively interfering with oncogenic proteins expressed on cancer cells. However, the long-term clinical benefit is often limited due to the emergence of drug resistance, frequently mediated by compensatory signaling pathways or immune es

Совпадение в полном тексте источника
… Unlike conventional immune responses, this mechanism is major histocompatibility complex (MHC)-independent, allowing bsAbs to be effective across a wide range of tumor types ( Figure 5 ) [ 78 , 79 ]. Figure 5 Mechanism of action of immune cell engagers (ICEs). … histocompatibility complex microsatellite instability-high mucin 16 neutralizing antibodies nanobodies natural killer no specific molecular profile objective response rate overall survival PARP inhibitors programmed cell death protein 1 programmed death-ligand 1 progression-free survival …

Challenges and new technologies in adoptive cell therapy.

Adoptive cell therapies (ACTs) have existed for decades. From the initial infusion of tumor-infiltrating lymphocytes to the subsequent specific enhanced T cell receptor (TCR)-T and chimeric antigen receptor (CAR)-T cell therapies, many novel strategies for cancer treatment have been developed. Owing to its promising outcomes, CAR-T cell therapy has revolutionized the field of ACTs, particularly for hematologic malignancies. Despite these advances, CAR-T cell therapy still has limitations in both autologous and allogeneic settings, including practicality and toxicity issues. To overcome these c

Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor Cells.

Cancer recurrence remains a great fear for many cancer survivors following their initial, apparently successful, therapy. Despite significant improvement in the overall survival of many types of cancer, metastasis accounts for ~90% of all cancer mortality. There is a growing understanding that future therapeutic practices must accommodate this unmet medical need in preventing metastatic recurrence. Accumulating evidence supports dormant disseminated tumor cells (DTCs) as a source of cancer recurrence and recognizes the need for novel strategies to target these tumor cells. This review presents

Совпадение в полном тексте источника
… Another mechanism by which DTCs were shown to evade the immune system is by downregulation of the expression of major histocompatibility complex class I protein (MHC-I), thus evading CD8+ T cell recognition ( 136 ). …

Novel immunotherapeutic approaches in gastric cancer.

Gastric cancer is a malignant tumor that ranks third in cancer-related deaths worldwide. Early-stage gastric cancer can often be effectively managed through surgical resection. However, the majority of cases are diagnosed in advanced stages, where outcomes with conventional radiotherapy and chemotherapy remain unsatisfactory. Immunotherapy offers a novel approach to treating molecularly heterogeneous gastric cancer by modifying the immunosuppressive tumor microenvironment. Immune checkpoint inhibitors and adoptive cell therapy are regarded as promising modalities in cancer immunotherapy. Food

Совпадение в полном тексте источника
… Abbreviations: APC, antigen presenting cell; CTLA4, cytotoxic T-lymphocyte associated protein 4; MHC, major histocompatibility complex; PD-L1, programmed death-ligand 1; PD1, programmed death-receptor 1; TCR, T cell receptor. Table 1. … Unlike αβ T cells, γδ T cells recognize antigens independently of major histocompatibility complex (MHC) presentation, demonstrating superior tissue penetration and lower cytokine secretion [ 68 ]. …

LAK to CIK continuum in glioma immunotherapy: a systematic review of efficacy and safety outcomes.

BACKGROUND: Immunotherapy against gliomas, including Glioblastoma multiform (GBM) as the most lethal type combines innate and adaptive immune responses to strengthen systemic and host-specific immunity. Among various cell-based immunotherapies, activated cell therapies utilize autologous immune cells activated ex vivo-such as lymphokine-activated killer (LAK) cells, cytokine-induced killer (CIK) cells, and cytotoxic T lymphocytes. Despite challenges, LAK laid the groundwork for further progress in activated killer cell therapies, such as CIK cells. CIK cells with their MHC-independent lytic ac

Совпадение в полном тексте источника
… LAK cells effectively target and eliminate a wide range of cancer cells, including those with low or no Major Histocompatibility Complex (MHC) expression. … Histocompatibility Complex World Health Organization Computed tomography Magnetic resonance imaging Positron emission tomography O⁶-Methylguanine-DNA Methyltransferase Chondroitin Sulfate Proteoglycan 4 Tumor microenviroment Natural killer group 2 member D Ubiquitin-Specific Protease 14 MHC …

Potential drug targets for Neuromyelitis optica spectrum disorders (NMOSD): A Mendelian randomization analysis.

BackgroundCertain peripheral proteins are involved in the development of Neuromyelitis optica spectrum disorders (NMOSD), such as IL-6, complement proteins, and MHC class II molecules. However, the roles of other new protein biomarkers are unclear. Current NMOSD treatments (e.g., intravenous pulse methylprednisolone, or satralizumab for IL-6 receptor inhibition) can only manage symptoms, necessitating the identification of new drug targets to treat NMOSD. The objective of this study is to identify potential drug targets for NMOSD through Mendelian randomization (MR) analysis, thereby addressin

Совпадение в полном тексте источника
… The inclusion criteria for pQTLs were: (i) genome-wide significance ( p < 5 × 10⁻⁸); (ii) independence based on a linkage disequilibrium (LD) threshold of r² < 0.001; (iii) cis-acting pQTLs; and (iv) localization outside the major histocompatibility complex (MHC) region (chr6, 26–34 Mb). …

Unravelling Osteoporosis: Key Genes and Potential Therapies.

Osteoporosis is a metabolic bone disease characterised by decreased bone mass and increased fracture risk, especially in aging women. Current treatments have limitations and side effects, prompting the need for novel therapeutic targets. Using Mendelian randomisation (MR) on the basis of GWAS data from the FinnGen consortium, we identified druggable genes associated with osteoporosis. Transcriptomic profiling, single-cell RNA sequencing (scRNA-seq) and immune infiltration analysis were employed to explore gene expression patterns and immune relevance. Gene set enrichment analysis and gene set

Совпадение в полном тексте источника
… Association Between Essential Genes and Immune Modulators We examined the correlation between key genes and diverse immune factors, such as immunosuppressive and immunostimulatory factors, major histocompatibility complex (MHC), chemokines and receptors. …

The emerging role of exosomes in innate immunity, diagnosis and therapy.

Exosomes, which are nano-sized transport bio-vehicles, play a pivotal role in maintaining homeostasis by exchanging genetic or metabolic information between different cells. Exosomes can also play a vital role in transferring virulent factors between the host and parasite, thereby regulating host gene expression and the immune interphase. The association of inflammation with disease development and the potential of exosomes to enhance or mitigate inflammatory pathways support the notion that exosomes have the potential to alter the course of a disease. Clinical trials exploring the role of exo

Совпадение в полном тексте источника
… The transplanted organ releases exosomes (allograft-exo) with donor major histocompatibility complex (MHC) molecules and they go out from the graft to the recipient’s lymphoid system ( 145 , 146 ). …

Targeting immunosenescence for improved tumor immunotherapy.

Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed "immunosenescence," which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underly

Nanobodies for Medical Imaging: About Ready for Prime Time?

Recent advances in medical treatments have been revolutionary in shaping the management and treatment landscape of patients, notably cancer patients. Over the last decade, patients with diverse forms of locally advanced or metastatic cancer, such as melanoma, lung cancers, and many blood-borne malignancies, have seen their life expectancies increasing significantly. Notwithstanding these encouraging results, the present-day struggle with these treatments concerns patients who remain largely unresponsive, as well as those who experience severely toxic side effects. Gaining deeper insight into t

Совпадение в полном тексте источника
… Similar to PD-1 and CTLA-4 checkpoint molecules, its function is to provide signals that downregulate T cell activity and replication, through a mechanism of interacting with the major histocompatibility complex II (MHC-II) molecules of APCs [ 107 ]. … A nanobody against mouse class II major histocompatibility complex (MHC) was developed and used to noninvasively image lymphoid organs and detect tumors. …

Unravelling T cell exhaustion through co-inhibitory receptors and its transformative role in cancer immunotherapy.

Persistent stimulation from cancer antigens leads to T lymphocytes (T cells) exhaustion, with up-regulated expression of co-inhibitory receptors, including programmed death-1 (PD-1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and mucin domain 3 (TIM-3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT). These receptors collectively impair T cell function via distinct molecular pathways, contributing to immune evasion and cancer progression. This review highlights the therapeutic promise of immune checkpoint inhibito

Совпадение в полном тексте источника
… Major histocompatibility complex (MHC) molecules on antigen‐presenting cells (APCs) present antigens to αβ T cells. … Characterization of the major histocompatibility complex class II binding site on LAG‐3 protein . P Natl Acad Sci USA . 1997 ; 94 : 5744 ‐ 5749 . doi: 10.1073/pnas.94.11.5744 PMC20850 9159144 70 Workman CJ , Dugger KJ , Vignali DAA . …

Перспективы Талкетамаба и его полезности в лечении множественной миеломы: безопасность, эффективность и место в терапии.

Несмотря на недавние достижения, большинство пациентов с множественной миэломой в конечном итоге развивают сопротивление имеющимся методам лечения, подчеркивая необходимость новых терапевтических стратегий. G Класс рецептора с протеиновыми соединениями C 5 Член D (GPRC5D) стал жизнеспособной новой терапевтической целью для клеток миэломы, которая привела к клиническому развитию талькетамаба, первого GPRC5D-directed bi специфичный Т-активист (TCE). В августе Талкетамаб получил ускоренное утверждение 2023 Управление по контролю за продуктами питания и лекарствами. Помимо ожидаемой краткосрочной

Совпадение в полном тексте источника
… Advantages of bispecific TCEs include their ability to promote T cell mediated tumor killing independent of T cell receptor-major histocompatibility complex interactions, and their “off-the-shelf” property, which allows for immediate clinical use (unlike CAR T cell therapy). 22 In 2023, the bispecific …

Systemic lupus erythematosus: pathogenesis and targeted therapy.

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by dysregulated immune responses and autoantibody production, which affects multiple organs and varies in clinical presentation and disease severity. The development of SLE is intricate, encompassing dysregulation within the immune system, a collapse of immunological tolerance, genetic susceptibilities to the disease, and a variety of environmental factors that can act as triggers. This review provides a comprehensive discussion of the pathogenesis and treatment strategies of SLE and focuses on the progress

Совпадение в полном тексте источника
… The major histocompatibility complex (MHC) genes, as well as components of the complement system such as C2 and C4, and tumor necrosis factor (TNF) genes TNFα and TNFβ, are located on chromosome 6. Polymorphisms within these genes have been shown to confer susceptibility to SLE [ 89 ]. … The inducible T cell co-stimulator (ICOS) on T cells increases after interaction with peptide-major histocompatibility complex (pMHC) in conjunction with CD28 co-stimulation. …

Redefining Chemoresistance: Natural Bioactives as Molecular Modulators at the Cancer-Tumor Microenvironment Interface.

Therapeutic resistance remains a critical barrier in effective cancer treatment, contributing to disease recurrence, progression, and reduced patient survival. In recent years, natural bioactive compounds have emerged as promising adjuncts in oncology due to their ability to modulate multiple biological processes involved in resistance. This review explores current evidence on the role of natural compounds in influencing cancer cell behavior and their interactions with the tumor microenvironment. By organizing these compounds into chemical families, we provide a structured overview of their po

Совпадение в полном тексте источника
… Tumor cells evade immune surveillance by downregulating tumor-associated antigens and major histocompatibility complex molecules, overexpressing immune checkpoint ligands, shedding antigens, and releasing immunosuppressive mediators such as TGF-β, IL-10, and PD-L1, resulting in cytotoxic T lymphocyte … Abbreviations—TME: tumor microenvironment; ECM: extracellular matrix; CAAs: cancer-associated adipocytes; MHC: major histocompatibility complex; CCL8: C-C motif chemokine ligand 8; MDSC: myeloid-derived suppressor cell; TGF-β: transforming growth factor beta; Treg: regulatory T cell; PD-L1: programmed …

Managing allorejection in off-the-shelf CAR-engineered cell therapies.

Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has revolutionized the treatment of various diseases, including cancers and autoimmune disorders. However, all US Food and Drug Administration (FDA)-approved CAR-T cell therapies are autologous, and their widespread clinical application is limited by several challenges, such as complex individualized manufacturing, high costs, and the need for patient-specific selection. Allogeneic off-the-shelf CAR-engineered cell therapy offers promising potential due to its immediate availability, consistent quality, potency, and scalability