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COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity.

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde

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… First, the major histocompatibility complex (MHC) on antigen presenting cells (APCs) is recognized by T cell receptors (TCRs) on antigen-specific T cells. Then, CD28 on T cells must send signals to APCs carrying CD80/CD86. …

Chimeric Antigen Receptor T-Cells: An Overview of Concepts, Applications, Limitations, and Proposed Solutions.

Adaptive immunity, orchestrated by B-cells and T-cells, plays a crucial role in protecting the body from pathogenic invaders and can be used as tools to enhance the body's defense mechanisms against cancer by genetically engineering these immune cells. Several strategies have been identified for cancer treatment and evaluated for their efficacy against other diseases such as autoimmune and infectious diseases. One of the most advanced technologies is chimeric antigen receptor (CAR) T-cell therapy, a pioneering therapy in the oncology field. Successful clinical trials have resulted in the appro

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… Upon capturing TAA’s, DCs get activated, express CCR7, mature, and 1) migrate to draining lymph nodes, 2) present the captured antigens to naïve CD4 + and CD8 + T-cells via the major histocompatibility complex (MHC) class I and II molecules, 3) express T-cell costimulatory molecules, for example, CD40 …

Эволюционный план лечения для пожилых пациентов с множественной миеломой: от квадских режимов до T-Cell Workers и CAR-T.

Множественная миелома (ММ) является главным образом болезнью пожилых людей. В последние годы резкое увеличение числа высокоэффективных методов лечения плазменных клеток привело к революции в уходе за престарелыми пациентами, страдающими миеломой (ММ), для которых слабые и связанные с возрастом конкурирующие причины смертности определяют управление. Традиционно лечение вновь диагностированных пожилых пациентов было сосредоточено на двойных или тройных комбинациях, состоящих из иммуномодуляторов (ИМИД), протеазонных ингибиторов (ИП), anti-CD38 моноклонные антитела (mAbs) и кортикостероиды, обесп

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… This dual binding facilitates an immunological synapse between T-cells and tumors cells [ 59 ], producing T-cell activation independent of major histocompatibility complex (MHC) restriction and without costimulatory signaling [ 59 , 60 , 61 ]. …

Cytopenias following anti-CD19 chimeric antigen receptor (CAR) T cell therapy: a systematic analysis for contributing factors.

BackgroundCytopenia is one of the most common adverse events following the CAR-T cell infusion, affecting the quality of life and potentially leading to life-threatening bleeding and infection. This study aimed to systematically review the cytopenias following anti-CD19 CAR-T therapy and further analyse the contributing factors.MethodsDatabases including PubMed, MEDLINE, Embase and Cochrane were systematically searched on 8 May 2022. A random-effect meta-analysis was used to estimate the incidence of cytopenia, and subgroup analyses were applied to explore heterogeneity.ResultsA total of 68 st

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… Introduction Genetically engineered T cells expressing chimeric antigen receptor (CAR), known as CAR-T cells, can recognize antigens specifically and activated directly without the need for antigen presentation by major histocompatibility complex (MHC) molecules. …

P2X7 Рецептор рентгеновских заболеваний: общие молекулярные механизмы и терапевтические последствия.

Редкие заболевания (РЛ) в индивидуальном порядке редко встречаются, но в совокупности они затрагивают большое число людей во всем мире, и подавляющее большинство из них по-прежнему не имеют эффективных методов лечения, позволяющих вести борьбу с заболеваниями. Благодаря достижениям в области геномики и платформ для обмена данными исследования все чаще переходят от одного заболевания к поиску конвергентных молекулярных путей, которые можно было бы использовать в различных клинически отличных друг от друга структурах. В этом контексте purinergic P2X7 рецептор (P2X7R) превратился в предполагаемую

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… Adenosine triphosphate-mediated signaling of P2X7 receptors controls donor extracellular vesicle release and major histocompatibility complex cross-decoration after allotransplantation . Am J Transplant . 2025 ; 25 ( 4 ): 674 – 681 . doi: 10.1016/j.ajt.2024.12.008 39694144 PMC11972886 86. …

Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.

Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells have emerged as a promising modern immunotherapeutic strategy, offering advantages over CAR-T cell therapy due to their innate cytotoxicity, safety profile, and potential for scalable, off-the-shelf allogeneic manufacturing. CAR-NK cells can be generated from multiple sources, with recent clinical studies demonstrating notable efficacy and lack of severe toxicity in hematologic malignancies. Nevertheless, the translation of this success to solid tumors is hampered by limited NK cell persistence, trafficking and infiltration c

Targeting myeloid villains in the treatment with immune checkpoint inhibitors in gastrointestinal cancer.

Despite the clinical outcomes being extremely limited, blocking immune inhibitory checkpoint pathways has been in the spotlight as a promising strategy for treating gastrointestinal cancer. However, a distinct strategy for the successful treatment is obviously needed in the clinical settings. Myeloid cells, such as neutrophils, macrophages, dendritic cells, and mast cells, are the majority of cellular components in the human immune system, but have received relatively less attention for the practical implementation than T cells and NK cells in cancer therapy because of concentration of the int

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… Tumor-specific CTLs are generated and activated via the immune complexes composed of the T-cell receptor (TCR) and antigen peptide-loading major histocompatibility complex molecule I/II (MHC I/II) expressed on antigen-presenting cells (APCs), such as DCs, B cells, and Møs. …

The Role of the CCR5 Receptor in Neuropathic Pain Modulation: Current Insights and Therapeutic Implications.

Neuropathic pain, a chronic condition arising from injury or dysfunction of the somatosensory nervous system, is characterized by persistent hypersensitivity and spontaneous pain. The chemokine receptor CCR5 (C-C motif chemokine receptor 5) has recently been identified as a critical mediator in neuroinflammation and neuropathic pain signaling pathways. Expressed on immune cells and neurons, CCR5 regulates immune cell recruitment and activation, thereby contributing to neuronal sensitization and maintenance of pain states. This review examines the currently characterized molecular mechanisms th

CAR-T: What Is Next?

The year 2017 was marked by the Food and Drug Administration (FDA) approval of the first two chimeric antigen receptor-T (CAR-T) therapies. The approved indications were for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and for the treatment of patients up to 25 years of age with acute lymphoblastic leukemia (ALL) that is refractory or in a second or later relapse. Since then, extensive research activities have been ongoing globally on different hematologic and solid tumors to assess the safety and efficacy of CAR-T therapy for these diseases. Limitations to CAR

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… Unlike T cells, CAR-T cells can recognize antigens on the surface of cancer cells without human major histocompatibility complex (MHC) molecules. Therefore, CAR-T cells can distinguish a wider range of targets than natural T cells. …

" Interleukin-27 " и " Аутоиммунные расстройства: компрессивный обзор иммунных функций " .

Аутоиммунные расстройства (АД) создают значительное бремя для здоровья и экономики во всем мире, характеризующееся ошибочной атакой иммунной системы организма на его собственные ткани. Хотя конкретные механизмы, лежащие в основе их развития, по-прежнему остаются неясными, речь идет о сочетании генетической предрасположенности (генетических предрасположений) и экологических факторов. Interleukin-27 (IL-27), среди многочисленных участвующих цитокинов, стал ключевым регулятором, выполняющим двойную роль в иммунной модуляции. Этот обзор погружается в молекулярную структуру и механизмы сигнализации

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… Major histocompatibility complex class I-deficient NOD-B2m null mice are diabetes and insulitis resistant. Diabetes. 1994;43:505–509. doi: 10.2337/diab.43.3.505. 84. …

In vitro расширила человека CD4+CD25+ регуляционные T клетки, подавляющие распространение Т клеток.

Регулирующие Т клетки (Tregs) оказались критически важными в балансе между автоиммунизацией и терпимостью и были связаны с несколькими аутоиммунными заболеваниями человека. Однако небольшое число трегов в периферии крови ограничивает их терапевтический потенциал. Поэтому мы разработали протокол, который позволит расширить "Трегз" при сохранении их подавляющей активности. Мы изолировали клетки CD4+CD25 hi от человеческой периферической крови и расширили их in vitro в присутствии anti-CD3 и anti-CD28 Магнитные кситы и высокие концентрации внешнего интерлейкина (IL) -2. Траги были эффективно расш

Ocular Manifestations Associated with Hematologic Malignancies: Mechanisms, Diagnosis, and Management.

Background: Hematologic malignancies (HMs), including leukemia and lymphoma, are systemic diseases that may cause a wide range of ocular manifestations. Methods: We searched PubMed/MEDLINE (2015-2026) and identified articles with an emphasis on clinically relevant studies and recent developments. Results: Clinically, ocular involvement presents with diverse manifestations, including retinal hemorrhage, vitreoretinal lymphoma, choroidal infiltration, orbital masses, treatment-related ocular toxicities, graft-versus-host disease, and secondary infectious complications. These findings may mimic o

CAR T-Cell Therapy for Patients with Multiple Myeloma: Current Evidence and Challenges.

The therapeutic landscape of multiple myeloma (MM) has benefited from an emergence of novel therapies over the last decade. By inducing T-cell kill of target cancer cells, chimeric antigen receptor (CAR) T-cell therapies have improved outcomes of patients with hematologic malignancies. B-cell maturation antigen (BCMA) is the current target antigen of choice for most CAR T-cell products under investigation for MM. However, their shortcomings deal with logistical and clinical challenges, including limited availability, manufacturing times, and toxicities. This article provides an overview of rec

TAM-ing the CIA-Tumor-Associated Macrophages and Their Potential Role in Unintended Side Effects of Therapeutics for Cancer-Induced Anemia.

Cancer-induced anemia (CIA) is a common consequence of neoplasia and has a multifactorial pathophysiology. The immune response and tumor treatment, both intended to primarily target malignant cells, also affect erythropoiesis in the bone marrow. In parallel, immune activation inevitably induces the iron-regulatory hormone hepcidin to direct iron fluxes away from erythroid progenitors and into compartments of the mononuclear phagocyte system. Moreover, many inflammatory mediators inhibit the synthesis of erythropoietin, which is essential for stimulation and differentiation of erythroid progeni

Constructing the cure: engineering the next wave of antibody and cellular immune therapies.

Immuno-oncology has revolutionized cancer treatment by mobilizing the immune system to eliminate tumors. Although immune checkpoint inhibitors and T cell therapies have mediated durable responses in hematologic malignancies and select solid tumors, most patients still relapse or fail to respond. To overcome these limitations, novel, next-generation immune constructs, including bispecific-cell therapy combinations, armored cells, tethered cytokines, immune-stimulatory antibody conjugates, and in vivo gene editing, are being developed to enhance specificity, persistence, and immune activation. T

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… Immune cell targets Most bispecific antibodies activate T cells via CD3, enabling major histocompatibility complex (MHC)-independent tumor recognition. While this broadens tumor targeting, this strategy is not limited to tumor-specific T cells and can induce systemic toxicity. …

The Role of TAM Receptors in Bone.

The TAM (TYRO3, MERTK, and AXL) family of receptor tyrosine kinases are pleiotropic regulators of adult tissue homeostasis maintaining organ integrity and self-renewal. Disruption of their homeostatic balance fosters pathological conditions like autoinflammatory or degenerative diseases including rheumatoid arthritis, lupus erythematodes, or liver fibrosis. Moreover, TAM receptors exhibit prominent cell-transforming properties, promoting tumor progression, metastasis, and therapy resistance in various cancer entities. Emerging evidence shows that TAM receptors are involved in bone homeostasis

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… A more recent study showed that major histocompatibility complex (MHC) class I chain-related protein A (MICA), a cell surface ligand for NKG2D mediating natural killer (NK) cell response, is regulated by the GAS6-TAM receptor axis in MM cells. …

T-cell redirecting bispecific antibodies in multiple myeloma: Current landscape and future directions.

T-cell engaging bispecific antibodies (BsAbs) have substantial activity in heavily pretreated patients with multiple myeloma (MM). The overall response rate obtained with B-cell maturation antigen (BCMA)-targeting BsAbs is approximately 60%-70%, including a high proportion of patients achieving very good partial response or complete response. Comparable efficacy is seen with BsAbs targeting GPRC5D or FcRH5. Cytokine release syndrome is frequently observed with BsAb treatment, but mostly during the step-up doses and the first full dose. Early intervention with IL-6 receptor blocking antibodies

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… In this way, the T cell is activated and can carry out effector functions, such as cytokine production and degranulation without the need for antigen presenting cells or major histocompatibility complex class I or class II molecules [ 14 ]. …

Management of Adverse Reactions for BCMA-Directed Therapy in Relapsed Multiple Myeloma: A Focused Review.

Anti-B-cell maturation antigen therapies consisting of bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T cells have shown promising results in relapsed refractory multiple myeloma (RRMM). However, the severe side effects include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia(s), infections, hemophagocytic lymphohistiocytosis, and organ toxicity, which could sometimes be life-threatening. This review focuses on these most common complications post-BCMA therapy. We discussed the risk factors, pathogenesis, clinical feat

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… These cells bind to tumor antigens in a major histocompatibility complex (MHC)-independent manner, resulting in cytotoxic T-cell mediated tumor lysis [ 23 ]. …

Immunotherapy-Associated Pancreatic Adverse Events: Current Understanding of Their Mechanism, Diagnosis, and Management.

Immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 (PD-1) and its ligand PD-L1 and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibodies, are involved in T cell-mediated immune response augmentation and promote anti-tumor immunity. Cancer patients treated with combination of immunotherapy, chemotherapy, radiotherapy, and targeted therapy exhibit superior clinical outcomes and tolerance compared with patients treated with monotherapies. However, immutherapy is associated with several concomitant immune-related adverse events (irAEs). For instance, IrAEs interfere

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… APC, antigen-presenting cell; MHC, major histocompatibility complex; TCR, T cell receptor. Mechanisms of the 3 immunotherapy agents are different from each other and ICIs alone or in combination with chemotherapy are conventional first- or second-line therapies. …

Esid 2014 oral presentations.

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