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Изучение роли Т клеток в болезни Альцгеймера и других нейродегенеративных заболеваниях: новые терапевтические идеи из Т Клеток на симпозиуме по мозгам.

В этой статье подытоживаются итоги первого симпозиума "Те ячейки в мозгу", проведенного в Колумбийском университете. Эксперты собрались для изучения роли Т клеток в нейродегенеративных заболеваниях. Ключевые темы включали характеристику антигенной иммунной реакции, репертуар T рецептора клеток (TCR), микробную этиологию болезни Альцгеймера (AD) и перекресток клеток микроглиа-Т с уделением особого внимания тому, как Т клетки влияют на нейроинфламмацию и АД биомаркеры, такие как амилоидная бета и тау. На симпозиуме были также рассмотрены иммунотерапии АД, включая исследование валацикловирусного

S1PR4-dependent Воздействие этрасимод на первичную активацию миэлоидных иммунных клеток человека.

ИСТОРИЯ ВОПРОСА: Sphingosine-1-phosphate (S1P) и его five Рецепторы S1PR1-5 играть важную роль в миграции, дифференциации и активации различных иммунных клеток. Недавно было утверждено несколько модуляторов S1PR с особой избирательностью для лечения различных подстрекательских заболеваний. Среди них Озанимод, S1PR1/5 Модулятор, утвержденный для лечения язвительного колита и множественных склерозов, и Etrasimod, S1PR1/4/5 Модулятор, утвержденный для лечения язвительного колита. Хронические самовоспалительные заболевания, такие, как вспыльчивые болезни кишечника (ББК) и язвительный колит, характ

Наномедицина - мощная терапия CAR-T для множественной миеломы: к программируемой, долговременной и точной иммунотерапии.

Множественная миелома (ММ) по-прежнему является трудновыполнимой гематологией. Несмотря на то, что терапия против созревания клеток B (BCMA), ориентированная на химерик антигенный рецептор Т-клектор (CAR-T), существенно углубила клиническую реакцию у пациентов с рецидивом/переносом MM, ее более широкое клиническое применение по-прежнему сдерживается рецидивом после лечения, недостаточной устойчивостью реакции, длительными сроками производства и ограниченной доступностью. Растущие данные свидетельствуют о том, что рецидив после лечения CAR-T в MM происходит не из одного механизма, а из конверге

Construction and validation of renal cell carcinoma tumor cell differentiation-related prognostic classification (RCC-TCDC): an integrated bioinformatic analysis and clinical study.

BackgroundRenal cell carcinoma (RCC) is a heterogeneous malignancy with diverse gene expression patterns, molecular landscapes, and differentiation characteristics of tumor cells. It is imperative to develop molecular RCC classification based on tumor cell differentiation for precise risk stratification and personalized therapy.MethodsWe obtained scRNA-seq profiles from GSE159115 and bulk RNA-seq profiles from TCGA-KIRC cohort. We then performed scRNA-seq cluster analysis, monocle2 pseudotime analysis, and prognostic analysis to obtain tumor cell differentiation-related prognostic genes (TCDGs

Collateral Victim or Rescue Worker?-The Role of Histone Methyltransferases in DNA Damage Repair and Their Targeting for Therapeutic Opportunities in Cancer.

Disrupted DNA damage signaling greatly threatens cell integrity and plays significant roles in cancer. With recent advances in understanding the human genome and gene regulation in the context of DNA damage, chromatin biology, specifically biology of histone post-translational modifications (PTMs), has emerged as a popular field of study with great promise for cancer therapeutics. Here, we discuss how key histone methylation pathways contribute to DNA damage repair and impact tumorigenesis within this context, as well as the potential for their targeting as part of therapeutic strategies in ca

Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.

Chimeric Antigen Receptor T (CAR-T) cell therapy has revolutionized cancer immunotherapy, particularly in hematological malignancies. However, the clinical application of autologous CAR-T cells faces significant high cost and manufacturing challenges. Universal allogeneic CAR-T cells, derived from healthy donors, represent a promising solution to these obstacles. These "off-the-shelf" therapies aim to reduce the complexity and cost of CAR-T production. Despite exciting advancements in genome-editing technologies and promising clinical trial data, significant challenges remain, including graft-

Chimeric antigen receptor (CAR) immunotherapy: basic principles, current advances, and future prospects in neuro-oncology.

With recent advances, chimeric antigen receptor (CAR) immunotherapy has become a promising modality for patients with refractory cancer diseases. The successful results of CAR T cell therapy in relapsed and refractory B-cell malignancies shifted the paradigm of cancer immunotherapy by awakening the scientific, clinical, and commercial interest in translating this technology for the treatment of solid cancers. This review elaborates on fundamental principles of CAR T cell therapy (development of CAR construct, challenges of CAR T cell therapy) and its application on solid tumors as well as CAR

Эпигенетическая ось Лактата-H4K12la-HDAC1 регулирует переход к микроглиальному состоянию во время экспериментального аутоиммунного энцефаломиелита у женских мышей.

Микроглиальная функциональная пластичность формируется метаболическим и эпигенетическим перепрограммированием, но то, как эти процессы регулируют автоиммунитет центральной нервной системы, остается неясным. Мы находим, что уровень цереброспинарной жидкости лактат коррелирует с множественным склерозом. Используя женские модели мыши экспериментального аутоиммунного энцефаломиэлита, аккумуляция спинного лакта приводит к стойкой микроглиальной гистоне лактилации, связывающей с гликолитической активацией. Микроглиавое исключение лактата дегидрогеназы А уменьшает эту лактиляцию и усугубляет остроту

Engineering Immunity: Current Progress and Future Directions of CAR-T Cell Therapy.

Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative form of immunotherapy, enabling the precise engineering of T cells to recognize and eliminate pathogenic cells. In hematologic malignancies, CAR-T cells targeting CD19 or B cell maturation antigens have achieved remarkable remission rates and durable responses in patients with otherwise refractory disease. Despite these successes, extending CAR-T cell therapy to solid tumors remains challenging due to antigen heterogeneity, poor T cell infiltration, and the immunosuppressive tumor microenvironment (TME). Beyond onco

Regulatory T cells and immune escape in HCC: understanding the tumor microenvironment and advancing CAR-T cell therapy.

Liver cancer, which most commonly manifests as hepatocellular carcinoma (HCC), is the sixth most common cancer in the world. In HCC, the immune system plays a crucial role in the growth and proliferation of tumor cells. HCC achieve immune escape through the tumor microenvironment, which significantly promotes the development of this cancer. Here, this article introduces and summarizes the functions and effects of regulatory T cells (Tregs) in the tumor microenvironment, highlighting how Tregs inhibit and regulate the functions of immune and tumor cells, cytokines, ligands and receptors, etc, t

Emerging Therapies for Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma (HCC) arises from hepatocytes and accounts for 90% of primary liver cancer. According to Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN) 2020, globally HCC is the sixth most common cancer and the third most common cause of cancer-related deaths. Reasons for HCC prognosis remaining dismal are that HCC is asymptomatic in its early stages, leading to late diagnosis, and it is markedly resistant to conventional chemo- and radiotherapy. Liver transplantation is the treatment of choice in early stages, while surgical resection, radiofrequency ablation (RFA) and

The landscape and trajectory of global CRISPR therapeutics.

With the first regulatory approval in 2023 of a CRISPR-based therapy for sickle cell disease followed by the recent demonstration of an accelerated, personalized CRISPR treatment for congenital severe carbamoyl-phosphate synthetase 1 deficiency, CRISPR-Cas9 genome editing has progressed from a laboratory technology into a clinical reality in just over a decade. While enthusiasm for deploying CRISPR-Cas9 to treat a range of human genetic diseases continues to grow, broad clinical application remains constrained due to technical, regulatory, manufacturing and economic challenges. Here, scientist

Совпадение в полном тексте источника
… Genome editing with CRISPR-Cas nucleases, base editors, transposases and prime editors Nat. Biotechnol. 38 2020 824 844 10.1038/s41587-020-0561-9 32572269 24 Alerasool N. Segal D. Lee H. Taipale M. An efficient KRAB domain for CRISPRi applications in human cells Nat. …

Chimeric antigen receptor modified T-cells for cancer treatment.

T cells engineered with the chimeric antigen receptor (CAR) are rapidly emerging as an important immunotherapy for hematologic malignancies. The anti-cluster of differentiation (CD)19 CAR-T cell therapy has been remarkably successful against refractory/relapsed acute lymphoblastic leukemia (ALL), and a complete remission rate as high as 90% was observed, in both children and adults. Although the achievement of clinical efficacy using CAR-T cell therapy for solid tumors has encountered several obstacles that were associated with the multiple mechanisms contributing to an immunosuppressive micro

Precision in Action: The Role of Clustered Regularly Interspaced Short Palindromic Repeats/Cas in Gene Therapies.

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated enzyme-CAS holds great promise for treating many uncured human diseases and illnesses by precisely correcting harmful point mutations and disrupting disease-causing genes. The recent Food and Drug Association (FDA) approval of the first CRISPR-based gene therapy for sickle cell anemia marks the beginning of a new era in gene editing. However, delivering CRISPR specifically into diseased cells in vivo is a significant challenge and an area of intense research. The identification of new CRISPR/Cas variants, particularly

Совпадение в полном тексте источника
… Class 2, type V includes miniature CRISPR-Cas 12J, CRISPR-Cas 12f, and CRISPR-associated transposase [ 17 , 18 , 19 ]. Studies have shown that type I CRISPR-Cas are newly emerging tools for transcriptome and genome manipulation in eukaryotic cells [ 20 , 21 ] and microbiota [ 22 ]. … RNA-guided DNA insertion with CRISPR-associated transposases Science 2019 365 48 53 10.1126/science.aax9181 31171706 PMC6659118 20. Dolan A.E. Hou Z. Xiao Y. Gramelspacher M.J. Heo J. Howden S.E. Freddolino P.L. Ke A. Zhang Y. …

Тонаберсат усиливает цитотоксичность в глиобластоме с помощью темозоломида путем нарушения межклеточной связи через коннексин 43 ингибирование.

Клетки глиобластомы зависят от коннексина 43 (Cx43) на основе данных о разрыве (GJs) для межклеточной связи, позволяющей им интегрироваться в широко разветвленную злокачественную сеть. Несмотря на многообещающие перспективы новой целевой терапии, отсутствие клинически осуществимых ингибиторов GJ препятствует их внедрению в клинической практике. В настоящем исследовании мы изучили тонаберсат (ТО) — лекарство, вызывающее кровоизлияние в мозг и имеющее свойства GJ-ингиберия, с точки зрения его способности разобрать межклеточную связь в сетях глиобластомы. Для изучения функциональной межклеточной

T cell immunotherapy for cervical cancer: challenges and opportunities.

Cancer cellular immunotherapy has made inspiring therapeutic effects in clinical practices, which brings new hope for the cure of cervical cancer. CD8+T cells are the effective cytotoxic effector cells against cancer in antitumor immunity, and T cells-based immunotherapy plays a crucial role in cellular immunotherapy. Tumor infiltrated Lymphocytes (TIL), the natural T cells, is approved for cervical cancer immunotherapy, and Engineered T cells therapy also has impressive progress. T cells with natural or engineered tumor antigen binding sites (CAR-T, TCR-T) are expanded in vitro, and re-infuse

Gene editing and CRISPR in the clinic: current and future perspectives.

Genome editing technologies, particularly those based on zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR (clustered regularly interspaced short palindromic repeat DNA sequences)/Cas9 are rapidly progressing into clinical trials. Most clinical use of CRISPR to date has focused on ex vivo gene editing of cells followed by their re-introduction back into the patient. The ex vivo editing approach is highly effective for many disease states, including cancers and sickle cell disease, but ideally genome editing would also be applied to diseases whic

The role of B2M in cancer immunotherapy resistance: function, resistance mechanism, and reversal strategies.

Immunotherapy has emerged as a preeminent force in the domain of cancer therapeutics and achieved remarkable breakthroughs. Nevertheless, the high resistance has become the most substantial impediment restricting its clinical efficacy. Beta-2 microglobulin (B2M), the light chain of major histocompatibility complex (MHC) class I, plays an indispensable part by presenting tumor antigens to cytotoxic T lymphocytes (CTLs) for exerting anti-tumor effects. Accumulating evidence indicates that B2M mutation/defect is one of the key mechanisms underlying tumor immunotherapy resistance. Therefore, eluci

GD2: hopes and challenges for the treatment of pediatric patients with tumors of the central nervous system.

Pediatric Central Nervous System (CNS) tumors are the leading cause of cancer-related death in children, yet effective treatment options remain limited. The tumor-associated antigen GD2 is a promising target for immunotherapeutic approaches aimed at treating pediatric CNS cancers; however, its heterogeneous expression within and between tumors can complicate the development of effective strategies. Here we review different aspects of GD2 biology, including its structure, synthesis pathway, and cellular and tissue expression, focusing on pediatric CNS tumors. We provide a detailed overview of t

Amyloids and the Heart: An Update.

Amyloids consist of fibrils that can be formed by a large variety of different precursor proteins. In localized amyloidosis, amyloids accumulate at the production site with a single organ being affected, whereas in systemic amyloidosis several organs are affected, with the heart being the most common, followed by the kidneys, liver, and the nervous system. The two most frequent systemic amyloidosis types affecting the heart in the vast majority (>95%) of cases are immunoglobulin light chain (AL) amyloidosis and transthyretin (TTR) amyloidosis (ATTR amyloidosis). Patients with amyloid cardiopat

Совпадение в полном тексте источника
… Genome editing with CRISPR-Cas nucleases, base editors, transposases and prime editors. Nat. Biotechnol. 2020;38:824–844. doi: 10.1038/s41587-020-0561-9. 137. Gupta D., Bhattacharjee O., Mandal D., Sen M.K., Dey D., Dasgupta A., Kazi T.A., Gupta R., Sinharoy S., Acharya K., et al. …