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CAR-T Therapies in Solid Tumors: Opportunities and Challenges.

Purpose of reviewThis review will discuss the challenges facing chimeric antigen receptor (CAR)-T cell application for solid tumors and opportunities to overcome these obstacles. In addition, this review will examine therapies that are in development for pediatric solid tumors.Recent findingsThe similar success of CAR-T cell treatment for hematological malignancies has not been observed in solid tumors because of the hostile tumor microenvironment and tumor heterogeneity. Most strategies developed to combat these limitations emphasize combinatorial techniques that still require further testing

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… Unlike conventional T cells, CARs function independently of the major histocompatibility complex (MHC), allowing for the recognition of a more extensive range of tumor-associated antigens [ 6 •]. CAR design has evolved over four generations to increase the efficacy of the therapy. …

Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward.

Chimeric antigen receptor T-cell (CAR-T) therapy has been successful in creating extraordinary clinical outcomes in the treatment of hematologic malignancies including relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). With several FDA approvals, CAR-T therapy is recognized as an alternative treatment option for particular patients with certain conditions of B-ALL, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, or multiple myeloma. However, CAR-T therapy for B-ALL can be surrounded by challenges such as various adverse events including the life

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… These effector cells combine the precise specificity of mAbs with the cytotoxicity of T lymphocytes, without the need for major histocompatibility complex (MHC); therefore, CAR-Ts are capable of selectively targeting cells proficient in the expression of the desired target antigen while remaining unreactive …

Histone modifications across cancers: mechanisms, therapy and clinical translation.

Cancer continues to be a major cause of death across the globe, and epigenetic dysregulation, including histone modifications, has been recognized as a major hallmark of cancer development, heterogeneity, and drug resistance. This review seeks to offer an overview of histone modifications in cancer, including the more studied histone modifications such as acetylation and methylation, as well as the less explored histone modifications such as phosphorylation, ubiquitination, and glycosylation. It also examines the role of histone modifications in the dysregulation of the three categories of enz

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… Abbreviations: BETi, bromodomain and extra-terminal inhibitor; EZH2i, enhancer of zeste homolog 2 inhibitor; HDACi, histone deacetylase inhibitor; ICB, immune checkpoint blockade; PARP, poly (ADP-ribose) polymerase; MHC-I, major histocompatibility complex class I; PD-1, programmed cell death protein … Abbreviations: BETi, bromodomain and extra-terminal inhibitor; EZH2i, enhancer of zeste homolog 2 inhibitor; HDACi, histone deacetylase inhibitor; ICB, immune checkpoint blockade; PARP, poly (ADP-ribose) polymerase; MHC-I, major histocompatibility complex class I; PD-1, programmed cell death protein …

Immune Therapies for Myelodysplastic Syndromes and Acute Myeloid Leukemia.

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies arising from the bone marrow. Despite recent advances in treating these diseases, patients with higher-risk MDS and AML continue to have a poor prognosis with limited survival. It has long been recognized that there is an immune component to the pathogenesis of MDS and AML, but until recently, immune therapies have played a limited role in treating these diseases. Immune suppressive therapy exhibits durable clinical responses in selected patients with MDS, but the question of which patients are most s

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… CAR T-Cell Therapies for MDS and AML Chimeric antigen receptor (CAR) T-cells are patient-derived T-cells transduced with viral vectors which express a chimeric antigen receptor for specific recognition of a tumor antigen, independent of major histocompatibility complex (MHC). …

Smart Lipid-Based Nanosystems for Therapeutic Immune Induction against Cancers: Perspectives and Outlooks.

Cancer immunotherapy, a promising and widely applied mode of oncotherapy, makes use of immune stimulants and modulators to overcome the immune dysregulation present in cancer, and leverage the host's immune capacity to eliminate tumors. Although some success has been seen in this field, toxicity and weak immune induction remain challenges. Liposomal nanosystems, previously used as targeting agents, are increasingly functioning as immunotherapeutic vehicles, with potential for delivery of contents, immune induction, and synergistic drug packaging. These systems are tailorable, multifunctional,

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… Abbreviations: MHC (major histocompatibility complex); CD (cluster of differentiation). 2.2. Shift of Immunotherapy Strategy The immune system and cancer progression are both highly intricate and heterogeneous, increasing the complexity in immunotherapy. … Abbreviations: PBS (Phosphate-buffered saline); DOX (doxorubicin); cGAMP (cyclic guanosine monophosphate-adenosine monophosphate); 93-O17S-F/cGAMP (the specific lipidoid nanoparticle used in this study); LNP (lipid nanoparticle); MHC (major histocompatibility complex); STING (stimulator of interferon …

CAR T-Cell Therapy for Cancer: Latest Updates and Challenges, with a Focus on B-Lymphoid Malignancies and Selected Solid Tumours.

Although exponential progress in treating advanced malignancy has been made in the modern era with immune checkpoint blockade, survival outcomes remain suboptimal. Cellular immunotherapy, such as chimeric antigen receptor T cells, has the potential to improve this. CAR T cells combine the antigen specificity of a monoclonal antibody with the cytotoxic 'power' of T-lymphocytes through expression of a transgene encoding the scFv domain, CD3 activation molecule, and co-stimulatory domains. Although, very rarely, fatal cytokine-release syndrome may occur, CAR T-cell therapy gives patients with ref

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… MHC (major histocompatibility complex) proteins present antigens in the form of peptide–MHC complexes to the T-cell receptor. …

Биоразлагаемый электроспун PLGA Nanofibers-Encapsolated Trichinella Sphiralis Antigens защищает от повторного использования экспериментального аутоиммунного энцефаломилита и связанного с ним микробиота дисбиоз.

ЦЕЛЬ: " Тричинелла спиралис " создала сложные механизмы иммуномодуляции при посредничестве экскременто-секретарских продуктов (ESL1), которые позволяют ей выжить в принимающей стране. Следовательно, антигены ESL1 обладают прекрасным потенциалом для лечения аутоиммунных заболеваний, таких, как множественный склероз (MS). Однако вопрос о том, могут ли своевременные контролируемые поставки антигенов ESL1 в vivo, как и в случае естественных инфекций, повысить его терапевтический потенциал в отношении MS, до сих пор неизвестен.Для этого мы ввели антигены ESL1 в полихлорированные (лактидно

Perspectives for the Use of CAR-T Cells for the Treatment of Multiple Myeloma.

During recent years considerable progress has been made in the treatment of multiple myeloma. However, despite the current improvements in the prognosis of this malignancy, it always ends with relapse, and therefore new therapy approaches for destroying resistant cancer cells are needed. Presently, there is great hope being placed in the use of immunotherapy against refractory/relapsed multiple myeloma which is unresponsive to any other currently known drugs. The most promising one is CAR-T cell therapy which has already shown tremendous success in treating other malignancies such as acute lym

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… Specific CAR-T cell binding to targeted cancer cells triggers their death without major histocompatibility complex restriction ( 13 ). …

The Problem of Molecular Target Choice for CAR-T Cells in Acute Myeloid Leukemia Therapy.

Recently, the chimeric antigen receptor (CAR)-T approach represented a breakthrough in the treatment of B-cell malignancies, encouraging the application of the approach for other hematological diseases, such as acute myeloid leukemia (AML). Heterogeneity and antigen variation in the pathological cell population hinder the choice of molecular targets in the case of AML. In this review, the critical aspects were described that are usually considered when selecting molecular targets for the new CAR genetic constructs. The role of AML-associated antigens in AML progression was covered. In conclusi

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… The natural ligands for the human NKG2D receptor are the major histocompatibility complex class I polypeptide–related sequence A and B proteins (MICA and MICB) and UL16 binding proteins (ULBP1–ULBP6). …

Extracellular RNA in melanoma: Advances, challenges, and opportunities.

Melanoma, a malignant mass lesion that originates in melanocytes and has a high rate of malignancy, metastasis, and mortality, is defined by these characteristics. Malignant melanoma is a kind of highly malignant tumor that produces melanin and has a high mortality rate. Its incidence accounts for 1%-3% of all malignant tumors and shows an obvious upward trend. The discovery of biomolecules for the diagnosis and treatment of malignant melanoma has important application value. So far, the exact molecular mechanism of melanoma development relevant signal pathway still remains unclear. According

Multiple Myeloma Therapy: Emerging Trends and Challenges.

Multiple myeloma (MM) is a complex hematologic malignancy characterized by the uncontrolled proliferation of clonal plasma cells in the bone marrow that secrete large amounts of immunoglobulins and other non-functional proteins. Despite decades of progress and several landmark therapeutic advancements, MM remains incurable in most cases. Standard of care frontline therapies have limited durable efficacy, with the majority of patients eventually relapsing, either early or later. Induced drug resistance via up-modulations of signaling cascades that circumvent the effect of drugs and the emergenc

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… CD74 is a glycoprotein found on the surface of the majority of PCs and is involved in the antigen presentation process by the major histocompatibility complex class II [ 162 , 163 ]. STRO-001 is a human anti-CD74 IgG fused with a potent maytansinoid warhead to two specific sites [ 164 ]. …

Current Uses of Mushrooms in Cancer Treatment and Their Anticancer Mechanisms.

Cancer is the leading cause of mortality worldwide. Various chemotherapeutic drugs have been extensively used for cancer treatment. However, current anticancer drugs cause severe side effects and induce resistance. Therefore, the development of novel and effective anticancer agents with minimal or no side effects is important. Notably, natural compounds have been highlighted as anticancer drugs. Among them, many researchers have focused on mushrooms that have biological activities, including antitumor activity. The aim of this review is to discuss the anticancer potential of different mushroom

Апиген как потенциальный модулятор нейроинфламмации в многоразовом склерозе: обзор.

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы (CNS), характеризующееся нейроинфламмацией и обезвоживанием. Несмотря на то, что в течение последнего десятилетия расширились возможности лечения MS, нынешняя терапия направлена главным образом на периферийные иммунные системы и часто связана со значительными побочными эффектами. Кроме того, эта терапия до сих пор не предлагает решений для последующего нейродегенерации, сопровождающего развитие болезни. Результаты исследований, проведенных с использованием клеточных и животных моделей и исследований

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… B cells function as potent antigen-presenting cells, sustaining encephalitogenic CD4+ T-cell responses via Major histocompatibility complex class II (MHC II)-mediated presentation of myelin and CNS-derived peptides [ 94 ]. …

The ubiquitin-proteasome system in the tumor immune microenvironment: a key force in combination therapy.

The ubiquitin-proteasome system (UPS) plays a crucial role in modulating the proliferation, activation, and normal functioning of immune cells through the regulation of protein degradation and function. By influencing the expression of immune checkpoint-associated proteins, the UPS modulates T cell-mediated anti-tumor immune responses and can potentially facilitate the immune escape of tumor cells. Additionally, the UPS contributes to the remodeling of the tumor immunosuppressive microenvironment (TIME) by regulating B cells, dendritic cells (DCs), macrophages, and Treg cells. Targeting the UP

Геномическая архитектура циркулирующих уровней цитокина указывает на цели лечения иммунных заболеваний.

Циркуляция цитокинес оркестрирует иммунную реакцию и является перспективной целью для лечения иммунных и подстрекательских заболеваний. Изучение генетической архитектуры циркулирующих уровней цитокина могло бы дать ключевые знания о причинно-следственных посредниках в связи с человеческими заболеваниями. Здесь мы провели исследования по общегеномной ассоциации (GWAS) 40 циркуляции цитокинов в мета-анализах 74,783 Люди. Мы обнаружили 359 между уровнями цитокина и вариантами 169 независимых лоси, включая 150 Транс- и 19 Носящая ножи лоси. Интеграция с транскриптивомными данными указывает на ключ

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… While most significant genes (78%) influenced the levels of a single cytokine, the genetically proxied expression of 54 genes showed an effect on circulating levels of up to 9 cytokines ( n [ SKI2 Subunit Of Superkiller Complex ; SKIV2L ] = 9, n [ Major Histocompatibility Complex, Class II, DR Beta 5 …

Chemokine receptors as important regulators of pathogenesis during arboviral encephalitis.

The central nervous system (CNS) is a highly complex network comprising long-lived neurons and glial cells. Accordingly, numerous mechanisms have evolved to tightly regulate the initiation of inflammatory responses within the brain. Under neuroinflammatory conditions, as in the case of viral encephalitides, the infiltration of leukocytes is often required for efficient viral clearance and recovery. The orchestration of leukocyte migration into the inflamed CNS is largely coordinated by a large family of chemotactic cytokines and their receptors. In this review, we will summarize our current un

Вирус Эпштейн-Барр, витамин D и иммунная реакция: связи с последствиями множественного склероза.

Множественный склероз (MS) — аутоиммунное заболевание центральной нервной системы (CNS) без какого-либо окончательного запуска. Однако эпидемиологические исследования показывают, что важными факторами риска являются такие экологические факторы, как инфекция вируса Эпштейн-Барр (ЭБВ) и низкий уровень витамина D (вид D) у генетически предрасположенных лиц. Одно из ведущих предложений заключается в том, что EBV приводит в действие MS с помощью таких механизмов, как молекулярная имитация, где активированные автоматически реактивные B и T лимфоциты ошибочно нацелены на самоантигены. В соответствии

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… The strongest genetic association is due to variation in major histocompatibility complex (MHC) (i.e., HLA) class II alleles DRB1*0101, DRB1*0602, and DRB1*1501 ( 5 ). …

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

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… Development Trajectory and Core Concepts of CAR-T-cell Therapy in Autoimmune Diseases CAR-T cells recognize and bind to antigens via antibody fragments in a major histocompatibility complex (MHC)-unrestricted manner, eliminating tumor cells. …

PPAR-γ in Melanoma and Immune Cells: Insights into Disease Pathogenesis and Therapeutic Implications.

Changes in skin pigmentation, like hyperpigmentation or moles, can affect appearance and social life. Unlike locally containable moles, malignant melanomas are aggressive and can spread rapidly, disproportionately affecting younger individuals with a high potential for metastasis. Research has shown that the peroxisome proliferator-activated receptor gamma (PPAR-γ) and its ligands exhibit protective effects against melanoma. As a transcription factor, PPAR-γ is crucial in functions like fatty acid storage and glucose metabolism. Activation of PPAR-γ promotes lipid uptake and enhances sensitivi

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… This leads to downregulation of major histocompatibility complex class I (MHCI) molecules and a reduction in their representation on the cell surface [ 293 ]. … histocompatibility complex class I MITF microphthalmia-associated transcription factor α-MSH α-melanocyte-stimulating hormone mTOR mechanistic target of rapamycin NCoA nuclear receptor coactivator NCoR nuclear receptor corepressor NFκB nuclear factor κB NRF2 nuclear factor erythroid 2-related factor …

Proteasome inhibitors - molecular basis and current perspectives in multiple myeloma.

Inhibition of proteasome, a proteolytic complex responsible for the degradation of ubiquitinated proteins, has emerged as a powerful strategy for treatment of multiple myeloma (MM), a plasma cell malignancy. First-in-class agent, bortezomib, has demonstrated great positive therapeutic efficacy in MM, both in pre-clinical and in clinical studies. However, despite its high efficiency, a large proportion of patients do not achieve sufficient clinical response. Therefore, the development of a second-generation of proteasome inhibitors (PIs) with improved pharmacological properties was needed. Rece