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From lab to lifesaver: the rise of CAR T-cell therapy in oncology.

BackgroundRecently, cancer treatment paradigms have shifted dramatically with the advent of immunotherapies, particularly chimeric antigen receptor (CAR) T-cell therapy. Despite it is revolutionary positive outcomes in treating hematologic malignancies, challenges such as severe toxicities, high treatment costs, and limited efficacy in solid tumors persist. This review highlights these limitations and the ongoing need for innovation in CAR T-cell therapy.Main bodyThis manuscript provides a comprehensive review of most current advancements in CAR T-cell therapy, with a focus on targeting its im

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… Moreover, CAR-T cells’ ability to fight cancer is enhanced by their ability of cancer cells to avoid recognition by the immune system by functioning outside involving major histocompatibility complex (MHC) molecules. … histocompatibility complex Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. …

Dietary fungi in cancer immunotherapy: From the perspective of gut microbiota.

Immunotherapies are recently emerged as a new strategy in treating various kinds of cancers which are insensitive to standard therapies, while the clinical application of immunotherapy is largely compromised by the low efficiency and serious side effects. Gut microbiota has been shown critical for the development of different cancer types, and the potential of gut microbiota manipulation through direct implantation or antibiotic-based depletion in regulating the overall efficacy of cancer immunotherapies has also been evaluated. However, the role of dietary supplementations, especially fungal

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… Traditionally, T cell activation depends on the interaction between TCR and specific antigens (including tumor cell-associated antigens) presented by the Major Histocompatibility complex (MHC) on the cell surface, which is frequently down-regulated by tumor cells ( 55 ). … Downregulation of major histocompatibility complex antigens in invading glioma cells: Stealth invasion of the brain . Lab Invest ( 2005 ) 85 ( 3 ): 328–41 . doi: 10.1038/labinvest.3700233 15716863 56 Sadelain M Brentjens R Rivière I . The basic principles of chimeric antigen receptor design . …

Устранение риска устойчивости к множественным склерозам: роль HLA-E*01 и инфекционный мононуклеоз в коорте населения.

Эпштейн-Барр Вирус (ЭБВ) и его клиническое проявление, инфекционный мононуклеоз (IM), тесно связаны с риском MS. Согласно недавнему исследованию in vitro, HLA-E*01::03в отличие от HLA-E*01::01, может защищаться от MS за счет более эффективной иммунной реакции против клеток, инфицированных ЭБВ. Однако роль ХЛА-Е*01 В НР по-прежнему нет ясности. МЕТОДЫ: Мы расследовали вопрос о том, может ли ХЛА-Е*01::01 был в значительной степени связан с повышенным риском MS у лиц с историей диагностирования IM с использованием 487,144 Люди из группы Биобанка Великобритании. Мы оценили взаимодействие между ХЛА

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… However, given the complexity of the major histocompatibility complex (MHC) region and the emphasis on HLA genes relevant to transplantation, the role of HLA‐E*01 in MS risk remains largely unexplored. …

Генетическое или терапевтическое нарушение траектории подачи сигналов Reelin/Apoer2 улучшает воспалительные результаты артрита.

Ремутатоидный артрит (RA) — хроническое аутоиммунное заболевание, характеризующееся синновальным воспалением, образованием паннуса и постепенным совместным разрушением. Вспыльчивая среда в RA приводит к активации эндотелиальных клеток и к повышению регулирования молекул сцепления, что облегчает проникновение лейкоцитов в синовый. Релин, циркулирующий гликопротеин, ранее связанный с активацией эндотели и вербовкой лейкоцитов для лечения таких заболеваний, как атеросклероз и множественный склероз, стал потенциальным регулятором этих процессов. Однако его роль в патогенезе РА остается слабой. Зде

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… K/BxN mice were generated by crossing KRN-C57BL/6 mice (obtained from Christophe Benoist), transgenic for a TCR recognizing a bovine ribonuclease peptide (RNase 42 to 56) presented by I-Ak major histocompatibility complex (MHC) class II molecule, with autoimmunity-prone nonobese diabetic NOD/ShiLtJ mice …

Новые горизонты для мультислерозовой терапии: 2025 и дальше.

Прогресс, достигнутый в борьбе с множественным склерозом (МС), представляет собой one о больших успехах современной молекулярной медицины. Развитие методов лечения с повышением избирательности и безопасности, руководствуясь достижениями в понимании фундаментальной иммунологии, нейробиологии, генетики и причин этой болезни, расширило традиционный акцент на лечении, добавив реальные возможности для профилактики и лечения. Здесь мы резюмируем последние достижения, которые вместе превратили эту болезнь из наиболее часто встречающегося в западном мире криппера на ее место сегодня как условие, в кот

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… B cells express major histocompatibility complex II (MHC II) molecules (as well as MHC I, which is expressed by all nucleated cells), allowing them to directly activate T cells. …

Динамическая съемка миелинской патологии в физиологически сохранившихся человеческих мозговых тканях с использованием третьей гармонической микроскопии.

Известно, что миелиновая патология играет центральную роль в таких расстройствах, как, в частности, множественный склероз (MS). Несмотря на это, патологические механизмы, лежащие в основе этих условий, часто трудно разгадать. Обычные методы, такие, как иммуноистохимия или подходы, основанные на красителях, не обеспечивают временной характеристики патофизиологических отклонений, вызывающих миелиновые изменения в образцах человека. Здесь, чтобы обойти эту обочину, мы представляем подход миелина к изображениям без ярлыков с живыми клетками, используя недавние достижения в нелинейной гармонической

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… Normal-appearing white matter (NAWM) was characterized as regions exhibiting typical levels of proteolipid protein (PLP) immunoreactivity distributed evenly across white matter areas, with an absence of major histocompatibility complex class II (MHC-II) immunoreactivity [ 31 ]. …

Summary of the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation.

The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation is intended to assist health care professionals worldwide who evaluate and manage potential candidates for deceased or living donor kidney transplantation. This guideline addresses general candidacy issues such as access to transplantation, patient demographic and health status factors, immunological and psychosocial assessment. The roles of various risk factors and comorbid conditions governing an individual's suitability for transpla

Генетический риск нейродегенеративных заболеваний связан с микрогилевыми путями, учитывающими конкретные заболевания.

Исследования, проведенные в рамках общегеномной ассоциации, выявили тысячи общих вариантов, связанных с повышенным риском нейродегенеративных расстройств. Однако некодирование этих вариантов затруднило назначение целевых генов для типов мозговых клеток. Геномические подходы, которые определяют хромосомную 3D-архитектуру, могут увязать некодирующие варианты риска и дистальные элементы регулирования генов, такие, как усилители, с пропагандистами генов. Используя карты улучшения взаимодействия для микроглии, нейронов и олигодендроцитов, мы определили конкретное обогащение генетической наследствен

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… For example, the major histocompatibility complex (MHC) was identified as a disease-risk locus in MS and schizophrenia ( Fig 3b ). …

Chimeric Antigen Receptor T Cell Therapy and Its Significance in Multiple Myeloma.

Multiple myeloma (MM) has a five-year prevalence worldwide of 230,000 people and is known as the second most common hematological malignancy within the United States. Extensive research has been conducted to gain a wide range of treatment strategies, providing hope to these patients. Combination therapy using chemotherapy, monoclonal antibodies, and immunomodulatory drugs are the current management of choice. After the introduction of chimeric antigen receptor (CAR) T cell therapy, promising results have been evidenced. In this therapy, T cells are derived from the patient and modified in-vitr

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… Patients of any human leukocyte antigen (HLA) type can be treated with CAR T cell therapy as the identification of tumor-specific antigen occurs without the influence of a major histocompatibility complex (MHC) [ 5 ]. …

Current challenges and emerging opportunities of chimeric antigen receptor-engineered cell immunotherapy.

Chimeric antigen receptor (CAR) engineered cellular immunotherapy offers the potential for precise targeting and elimination of tumor cells, providing a tailored approach to cancer treatment. CAR-T cells demonstrate significant anti-tumor activity among these therapies. Nonetheless, these therapies may trigger adverse effects, including inflammatory and neurotoxic reactions during treatment. Recent efforts have been directed toward enhancing efficacy by optimizing CAR design or modulating its activity. Compared to CAR-T cells, CAR-engineered natural killer cells (CAR-NK) present notable advant

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… The first is an antigen-specific signal, which is triggered when the T cell receptor (TCR) recognizes a specific peptide presented by the major histocompatibility complex (MHC) on antigen-presenting cells. … Food and Drug Administration Cytokine Release Syndrome CAR-engineered Natural Killer Cell CAR-macrophage T Cell Receptor Major Histocompatibility Complex Single-Chain Variable Fragment Acute Lymphoblastic Leukemia Relapsed and Refractory Diffuse Large B Cell Lymphoma B-cell Precursor ALL Mantle …

Прогнозирование аутоиммунных заболеваний на основе глубокого обучения.

Аутоиммунные заболевания представляют собой сложную группу заболеваний, вызванных иммунной системой, ошибочно наносящей удар по тканям тела. Их этиология включает в себя множество факторов, таких, как генетика, экологические факторы и аномалии в иммунных клетках, что затрудняет прогнозирование и лечение. Т клетки как один из ключевых компонентов иммунной системы играют важнейшую роль в иммунной системе человека и оказывают значительное воздействие на патогенез аутоиммунных заболеваний. Ряд исследований показали, что рецепторы Т-клеток (ТКР) могут быть вовлечены в патогенез различных аутоиммунн

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… CDR1 and CDR2 are encoded by the V-gene, and are essential for the interaction of the TCRs with the Major Histocompatibility Complex (MHC) complexes. …

Chimeric antigen receptor T cell therapy for the treatment of systemic rheumatic diseases: a comprehensive review of recent literature.

Systemic rheumatoid diseases (SRDs) are autoimmune and inflammatory disorders that affect multiple organ systems, impacting patients' quality of life, and survival rates. Standard treatment requires continuous drug therapy and immunosuppression. Chimeric antigen receptor (CAR) T cell therapy has the potential to target and eliminate pathologically activated immune cells and re-establish tolerance in organs affected by dysregulated immunity, making them a promising treatment option for autoimmune diseases. In autoimmune diseases, CAR T cells have the advantage of being able to kill B cells effe

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… Moreover, studies have also described the use of two different CAR T cell approaches for the treatment of autoimmune diabetes in which a CAR molecule was designed based on an antibody that recognizes the major histocompatibility complex (MHC) class II: peptide complex, which was linked to Cluster of …

Teclistamab: First Approval.

Teclistamab (TECVAYLI®), a bispecific antibody that targets CD3 and B cell maturation antigen (BCMA), is being developed by Janssen Research and Development for the treatment of relapsed or refractory multiple myeloma. Teclistamab was recently granted conditional approval in the EU for the treatment of adult patients with relapsed and refractory multiple myeloma who have received three or more prior therapies (including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody) and have demonstrated disease progression on the last therapy. Teclistamab was subsequently approve

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… This process is non-specific and does not involve major histocompatibility complex class 1 molecules on antigen-presenting cells [ 3 ]. …

Safety and efficacy of autologous tumour cell vaccines as a cancer therapeutic to treat solid tumours and haematological malignancies: a meta-analysis protocol for two systematic reviews.

IntroductionAutologous cancer cell vaccines are promising personalised immunotherapeutic options for solid and haematological malignancies that uses the patient's own cells to arm an immune response. Evidence suggests that among patients receiving these vaccines, those who mount an immune response against their own tumour cells have better prognosis, and a myriad of preclinical studies have demonstrated the same. Recently, two autologous cell vaccines Vigil and OncoVAX have made it to phase III clinical trials. Here, we outline a protocol to be used for two separate systematic reviews using a

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… However, increased mutation rates prevalent in tumours may lead to downregulation of these antigens or reduce their presentation on major histocompatibility complex class I (MHC-I) allowing tumours to escape an oligoclonal generated response. 5 6 As such, for effective cancer therapy, the need to target …

Juvenile-onset Systemic Lupus Erythematosus: Recent Advances in Pathogenesis and Treatment.

PURPOSE OF REVIEW: This review summarizes recent advances in understanding the pathogenesis and therapeutic landscape of juvenile-onset systemic lupus erythematosus (jSLE), with a focus on how emerging genetic and immunologic insights inform patient stratification, targeted treatments, and Treat-to-Target (T2T) approaches in pediatric care. RECENT FINDINGS: Studies of (ultra-)rare gene variants (e.g., affecting TLR7, UNC93B1, PLD4, PTPN2, BACH2) aided in understanding key pathogenic pathways, and allowed linking these to associated clinical phenotypes. Multi-ancestral genomic studies and cumu

Toxicities of CAR T-cell therapy: a review of current literature.

The chimeric antigen receptor (CAR) design, first invented by Zelig Eshhar, paved the way for the use of genetically modified T-cells in targeted therapy against cancer cells. Since then, it has gone through many generations, especially with the integration of co-stimulation in the second and third-generation CARs. However, it also mounts a hyperactive immune response named as cytokine release syndrome with the release of several cytokines eventually resulting in multiple end-organ toxicities. The severity of cytokine release syndrome depends upon certain factors such as the tumor burden, choi

Cancer Vaccines and Beyond: The Transformative Role of Nanotechnology in Immunotherapy.

Cancer is one of the leading causes of morbidity and mortality globally, responsible for approximately 10 million deaths in 2022 and an estimated 21 million new cases in 2024. Traditional cancer treatments such as surgery, radiation therapy, and chemotherapy often present limitations in efficacy and side effects. However, immunotherapeutic vaccines have emerged as a promising approach, leveraging the body's immune system to target and eliminate cancer cells. This review examines the evolving landscape of cancer vaccines, differentiating between preventive and therapeutic strategies and highlig

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… Also, a hallmark of tumor immune evasion is the downregulation or loss of tumor-specific antigens (TSAs) and major histocompatibility complex (MHC) molecules on the surface of cancer cells. This downregulation prevents effective antigen presentation to cytotoxic T lymphocytes (CTLs). …

Impact of clinical factors and allograft leukocyte content on post-transplant lymphopenia, monocytopenia, and survival in patients undergoing allogeneic peripheral blood haematopoietic cell transplant.

BackgroundWe have previously shown that lymphopenia and monocytopenia at 2-3 months post-allogeneic haematopoietic cell transplant (HCT) is associated with poor survival in recipients of both myeloablative and reduced intensity conditioning regimens. It is not known whether the graft leukocyte content has a role in early lymphocyte and monocyte recovery following allogeneic T-cell replete peripheral blood HCT.MethodsHaematologic recovery data, including absolute lymphocyte and monocyte counts (ALC and AMC, respectively) at day +15, +30, +60, and +100, and outcomes data were pooled from two pri

Potential Immunotherapy Targets for Liver-Directed Therapies, and the Current Scope of Immunotherapeutics for Liver-Related Malignancies.

Liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is increasing in incidence and mortality across the globe. An improved understanding of the complex tumor microenvironment has opened many therapeutic doors and led to the development of novel pharmaceuticals targeting cellular signaling pathways or immune checkpoints. These interventions have significantly improved tumor control rates and patient outcomes, both in clinical trials and in real-world practice. Interventional radiologists play an important role in the multidisciplinary team given their expertise

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… Signaling of CD40 on DCs stimulates the production of pro-inflammatory cytokines such as IL-6, promotes induction of other co-stimulatory molecules, and provides stability towards the major histocompatibility complex-antigen complex [ 198 , 199 ]. … Decreased expression of B7 costimulatory molecules and major histocompatibility complex class-I in human hepatocellular carcinoma. J. Gastroenterol. Hepatol. 2004;19:1121–1127. doi: 10.1111/j.1440-1746.2004.03467.x. 20. …

Включаю T-камеры для очистки.

Те, кто занимается клетками, представляют собой преобразующий подход к иммунотерапии рака, стимулирующий использование двухуровневых и многообразных антителных конструкций для перенаправления китотоксичности Т-клеток на злокачественные клетки. Эти молекулы соединяют клетки Т и клетки опухоли, одновременно связывая CD3 с Т клетками и связанными с опухолью антигенами на раковые клетки, что позволяет точно определить иммунную направленность даже в иммунологических "холодных" опухолях. Последние достижения включают в себя условное использование Т-клеток, активированное микроэкологическими протезам

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… TAA, tumor-associated antigen; scFv, single-chain variable fragment; CD3, cluster of differentiation 3; pMHC, peptide+major histocompatibility complex; scTCR, single-chain T-cell receptor; CD28, cluster of differentiation 28; ICI, immune-checkpoint inhibitor. …