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Recombinant Oncolytic Viruses: Hexagonal Warriors in the Field of Solid Tumor Immunotherapy.

In the past decade, research on recombinant oncolytic viral agents in the treatment of solid tumors has evolved from the initial stage of simple genetic engineering to the current stage of multiple pipelines of parallel clinical application and combination therapy. Compared with T-VEC, the classical therapeutic agent that only expresses GM-CSF, which was approved in 2015, most new oncolytic virus designs include diverse gene constructs to reduce toxic effects, enhance multiple antitumor immunity, avoid immune clearance, or enhance tumor targeting. The single route of administration that activa

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… ICP47 inhibits the stabilization and translocation of major histocompatibility complex class I (MHC-I) antigenic peptides into the Golgi apparatus, which are necessary in CD8 + cytotoxic T lymphocyte (CTL) immune surveillance [ 80 ]. … histocompatibility complex class I MPA | Metastatic pancreatic cancer NAb | Neutralizing antibody NK cells | Natural killer cells NMIBC | Non-muscle-invasive bladder cancer ORR | Objective response rate OV | Oncolytic virus PDAC | Pancreatic ductal adenocarcinoma S100A1 | S100 calcium-binding protein …

Immunotherapy for Cutaneous Squamous Cell Carcinoma: Results and Perspectives.

Although initial surgical excision cures 95% of patients, a minority of cutaneous squamous cell carcinomas (cSCCs) are judged to be unresectable, either locally advanced or with unresectable regional lymph nodes or distant metastases. These patients are offered systemic treatments. Response rate to chemotherapy is relatively low and not durable, as well as the results obtained with epidermal growth factor inhibitors (EGFRi). Like other cutaneous tumors, cSCCs have high immunogenicity, driven by the high mutational burden, the ultraviolet signature, and the overexpressed tumor antigens. Two che

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… Preclinical and clinical investigations revealed a complex interplay between radiotherapy, irradiated cells and tissues, and the immune system ( 44 – 46 ); for example, exposure to radiotherapy was shown to upregulate major histocompatibility complex I (MHC I) expression in tumor cells, modulate immunosuppressive …

Тригеминальный контакт с артерией у людей, не имеющих тригеминиальной нейронгии - исследование MR.

Основная цель этого исследования состоит в том, чтобы предложить новую нервную сеть, названную BrainNeXt, для автоматизированного обнаружения расстройств мозга с использованием изображений магнитного резонанса (MRI). Кроме того, мы намерены изучить функционирование нашей предлагаемой сети по различным видам медицинского применения. Для обеспечения эффективности классификации изображений с высоким/громким изображением мы собрали новый набор данных МРТ, принадлежащих four Классы:1Болезнь Альцгеймера,2) хроническая ишемия,3) множественный склероз и ()4) контроль. Вдохновленные ConvNeXt, мы спроек

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… LAG-3 shares high homology with CD4 [ 46 ], is highly expressed on Tregs [ 47 ], and has a high affinity for major histocompatibility complex class II (MHC II). …

The Role of Intravesicular Proteins and the Protein Corona of Extracellular Vesicles in the Development of Drug-Induced Polyneuropathy.

Extracellular vesicles (EVs) as membrane structures of cellular origin participating in intercellular communication are involved in the molecular mechanisms of the development of various variants of polyneuropathy. Taking into account the increasing role of the protein corona of EVs and protein-protein interactions on the surface of EVs in the pathogenesis of various diseases, we focused our attention in this review on the role of intravesicular proteins and the protein corona of EVs in the development of chemotherapy-induced polyneuropathy (CIPN). It has been shown that EVs are effectively in

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… Exosomes produced by professional and nonprofessional antigen-presenting cells contain a large number of major histocompatibility complexes MHC, which suggests that exosomes have an antigen-presenting function [ 78 ]. …

Choice of Unmanipulated T Cell Replete Graft for Haploidentical Stem Cell Transplant and Posttransplant Cyclophosphamide in Hematologic Malignancies in Adults: Peripheral Blood or Bone Marrow-Review of Published Literature.

Allogeneic hematopoietic stem cell transplantation (SCT) is often the only curative option for many patients with malignant and benign hematological stem cell disorders. However, some issues are still of concern regarding finding a donor like shrinking family sizes in many societies, underrepresentation of the ethnic minorities in the registries, genetic variability for some races, and significant delays in obtaining stem cells after starting the search. So there is a considerable need to develop alternate donor stem cell sources. The rapid and near universal availability of the haploidentical

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… Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide Blood 2001 98 12 3456 3464 10.1182/blood.V98.12.3456 2-s2.0-0035761436 11719388 18 Nomoto K. …

Osteoporosis: the current status of mesenchymal stem cell-based therapy.

Osteoporosis, or bone loss, is a progressive, systemic skeletal disease that affects millions of people worldwide. Osteoporosis is generally age related, and it is underdiagnosed because it remains asymptomatic for several years until the development of fractures that confine daily life activities, particularly in elderly people. Most patients with osteoporotic fractures become bedridden and are in a life-threatening state. The consequences of fracture can be devastating, leading to substantial morbidity and mortality of the patients. The normal physiologic process of bone remodeling involves

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… A comparative study of human derived-MSCs demonstrated that Wharton’s jelly-derived MSCs (WJ-MSCs) exhibited the strongest inhibitory effects on T cell proliferation and the weakest expression of immune-related genes, such as genes encoding major histocompatibility complex (MHC) II and human leukocyte … histocompatibility complex; MSC, mesenchymal stem cell; NOG, noggin; OPG, osteoprotegerin; OSX, osterix; OVX, ovariectomy; PDGF-B, platelet-derived growth factor B; PL, placenta-derived; PPARγ, peroxisome proliferator-activated receptor gamma; PTH1R, parathyroid hormone 1 receptor; RANKL, receptor activator …

Нейроинфламмация в нейродегенеративных заболеваниях: сосредоточение внимания на посредничестве лимфоцитов T.

Нейродегенеративные заболевания представляют собой группу заболеваний, характеризующихся постепенным ухудшением центральной нервной системы, что приводит к снижению когнитивных, моторных и эмоциональных способностей пациентов. Нейроинфламмация играет важную роль в развитии этих заболеваний. Вместе с тем исследования терапевтических подходов к целенаправленной борьбе с нейроинфламмацией носят ограниченный характер. Все шире признается роль лимфоцитов, которые являются важнейшими посредниками адаптивной иммунной реакции, в нейродегенеративных заболеваниях. В настоящем обзоре основное внимание уд

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… The first signal is produced when T cell receptors recognize a complex formed by an antigen and major histocompatibility complex class II (Basu et al., 2013; Figure 1 ). The second signal occurs when a matching ligand on the surface of the T cell binds to a co-stimulatory molecule on the APC. … APC: Antigen-presenting cell; FoxP3: forkhead box P3; GATA3: binding protein 3; IFN-γ: interferon-gamma; IL: interleukin; MHC: major histocompatibility complex; RORγ: retinoic acid-related orphan receptor gamma; STAT5: signal transducer and activator of transcription 5; T-bet: T-box expressed in T cells …

CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.

CRISPR-Cas9 has progressed from an experimental tool to a therapeutic modality, marked by the first regulatory approvals of an ex vivo-edited autologous CD34+ hematopoietic stem cell product that induces fetal hemoglobin (CASGEVY/exa-cel). In this narrative review, we synthesize modality-specific molecular diagnostic strategies used across early CRISPR clinical translation. In parallel, early clinical experience has begun to demonstrate the feasibility of in vivo editing, including subretinal delivery for CEP290-associated inherited retinal degeneration (EDIT-101 programme) and hepatocyte-targ

The Molecular Aspect of Antitumor Effects of Protease Inhibitor Nafamostat Mesylate and Its Role in Potential Clinical Applications.

Nafamostat mesylate (NM), a synthetic serine protease inhibitor first placed on the market by Japan Tobacco in 1986, has been approved to treat inflammatory-related diseases, such as pancreatitis. Recently, an increasing number of studies have highlighted the promising effects of NM in inhibiting cancer progression. Alone or in combination treatments, studies have shown that NM attenuates various malignant tumors, including pancreatic, colorectal, gastric, gallbladder, and hepatocellular cancers. In this review, based on several activating pathways, including the canonical Nuclear factor-κB (N

Advancing Multiple Myeloma Immunotherapy: A Review of Chimeric Antigen Receptor T-Cell and Bispecific T-Cell Engagers Cell Therapies in Revolutionizing Treatment.

Multiple Myeloma (MM) is a hematologic malignancy characterized by clonal plasma cell development, leading to serious complications. Despite traditional treatments, MM remains incurable, necessitating innovative therapeutic approaches. Chimeric Antigen Receptor (CAR) T-cell therapy and Bispecific T-cell engagers (BiTEs) are emerging immunotherapies showing promise in MM treatment. CAR T-cell therapy involves modifying patient T-cells to target specific antigens, primarily B Cell Maturation Antigen (BCMA). BiTEs, on the other hand, are non-IgG-like bispecific antibodies designed to engage both

T-Cell Aptioners in Multieloma: Клинический обзор.

Технологи T-клеток (TCE) сконструированы таким образом, чтобы связывать как субъект CD3 на Т-клетки, так и конкретные антигены на клетки опухоли, вызывая активацию Т-клеток и лизиз клеток опухоли. TCE, предназначенные для антигена созревания клеток В (BCMA) и рецептора с соединениями G-протеинов, класс C, группа 5, член D (GPRC5D) продемонстрировал значительную клиническую активность у пациентов, прошедших интенсивную предварительную обработку, с множественным миеломой (RRMM). В качестве монотерапии ПТО имеют общий коэффициент ответов (ОРС) выше 60%, с глубокими и прочными гематологическими ре

The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand?

Immune checkpoint inhibitors (ICIs) are a novel class of immunotherapy drugs that have improved the treatment of a broad spectrum of cancers as metastatic melanoma, non-small lung cancer or renal cell carcinoma. These humanized monoclonal antibodies target inhibitory receptors (e.g. CTLA-4, PD-1, LAG-3, TIM-3) and ligands (PD-L1) expressed on T lymphocytes, antigen presenting cells and tumor cells and elicit an anti-tumor response by stimulating immune system. Nevertheless, the improved overall survival is complicated by the manifestation of Immune-related Adverse Effects (irAEs). During treat

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… APC, Antigen Presenting Cells; MHC-Ag, Major Histocompatibility Complex with tumor antigen; CTLA-4, Cytotoxic T-Lymphocyte Antigen 4; PD-1, Programmed cell death protein 1; PD-L1, Programmed death-ligand 1. … histocompatibility complex (MHC). …

Genomics of Smoldering Multiple Myeloma: Time for Clinical Translation of Findings?

Smoldering multiple myeloma (SMM) is an asymptomatic disorder of clonal bone marrow (BM) plasma cells (PCs) in between the premalignant condition known as monoclonal gammopathy of undetermined significance and overt multiple myeloma (MM). It is characterized by a deep biological heterogeneity that is reflected in a markedly variable progression risk among patients. Recently proposed risk stratification models mainly rely on indirect markers of disease burden and are unable to identify cases in whom clonal PCs have already undergone the "malignant switch" but major clonal expansion has not occu

Antibody-Drug Conjugates for Multiple Myeloma: Just the Beginning, or the Beginning of the End?

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen

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… Targeting CD74 CD74 is a non-polymorphic type II transmembrane glycoprotein that functions as a major histocompatibility complex (MHC) class II chaperone, and participates in other non-MHC protein trafficking, such as of angiotensin II type I receptor [ 82 ]. … histocompatibility complex; MMAE, monomethyl auristatin E; MMAF, monomethyl auristatin F; MRD, minimal residual disease; MTD, maximum tolerated dose; ORR, overall response rate; OS, overall survival; Pd, pomalidomide and dexamethasone; PFS, progression-free survival; PIs, proteasome inhibitors; RP2D …

Роль растворимых биомаркеров в лечении множественных склерозов и нервно-воспалительных заболеваний.

Множественный склероз (MS) представляет собой сложное хроническое заболевание с иммунной помощью, характеризующееся острым и прогрессивным воспалительным повреждением центральной нервной системы. MS проявляется клинически с непредсказуемыми неврологическими симптомами в результате точечных провокационных атак, а также постепенного нейродегенерации, что в значительной степени способствует долгосрочному развитию инвалидности. По мере развития методов лечения разработка более индивидуализированных стратегий охватывает различные механизмы травмирования, которые могут быть целенаправленными или про

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… Of the potential genetic risk states for autoimmunity, major histocompatibility complex (MHC) haplotypes have been among the most studied. …

Методы машинного обучения для классификации множественного склероза и болезни Альцгеймера с использованием геномных данных.

Сложные заболевания создают трудности в прогнозировании из-за их многофакторного и полигенного характера. В этом исследовании используется машинное обучение (ML) для анализа геномных данных из британского биобанка с целью прогнозирования геномной предрасположенности к таким сложным болезням, как множественный склероз (MS) и болезнь Альцгеймера (AD). Мы проверили логистическую регрессию (LR), методы ансамбля деревьев и модели глубокого обучения с этой целью. LR продемонстрировал замечательную стабильность в различных поднаборах данных, превосходя глубинные подходы к обучению, которые продемонст

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… The HLA-A gene belongs to the major histocompatibility complex (MHC) class I. It is worth noting that the most significant genetic factor associated with MS, as reported in the literature, is HLA-DRB1*15:01 [ 30 ], which is a predisposing HLA variant belonging to the MHC class II. …

Exploring the Vasculitis-Tumors Link: Epidemiological Patterns, Mechanistic Insights, and Clinical Implications.

This review systematically examines the association between vasculitis and malignancies by summarizing the risk of tumor-associated vasculitis, their clinical characteristics, and proposed pathogenic mechanisms across different vasculitic subtypes. Relevant case reports and mechanistic studies are integrated to provide a comprehensive overview of this entity. The findings offer practical value for rheumatologists in distinguishing primary vasculitis from malignancy-associated forms and optimizing patient surveillance, and for oncologists in improving recognition of tumor-associated vasculitis

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… Masuda T., Ito H., Hirata J., et al., “Fine Mapping of the Major Histocompatibility Complex Region and Association of the HLA‐B*52:01 Allele With Cervical Cancer in Japanese Women,” JAMA Network Open 3, no. 10 (2020): 2023248. 51. …

Breathing new life into T-cell receptor-engineered T-cell therapy in solid tumors: enhancing strategies to expand the universality of precision therapy.

Adoptive T-cell transfer therapy (ACT) has significantly propelled the advancement of tumor immunotherapy. Among various strategies targeting solid tumors, the T-cell receptor (TCR)-engineered T-cell (TCR-T cell) therapy has emerged as a highly promising approach, exhibiting an expanded therapeutic window across diverse patient populations and superior tumoricidal activity in certain solid malignancies compared with chimeric antigen receptor T cell (CAR-T) and tumor-infiltrating T cells/lymphocyte (TIL) therapies. However, its clinical efficacy remains constrained. In this paper, we introduce

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… When TCR binds to its homologous peptide-major histocompatibility complex (pMHC) compound, associated CD247 (CD3ζ) chains dimerize to initiate downstream signaling, leading to rapid gene expression driven by transcription factors NF-κB, AP-1, and NFAT, exerting direct cytotoxic effects on target cells …

Efficacy and safety of combined RANKL and PD-1 inhibitors in bone metastases: a retrospective study.

BackgroundRANKL inhibitors can inhibit the formation and functional activation of osteoclasts, providing osteoprotective effects. Recent findings indicate that RANKL inhibitors also exhibit immunomodulatory effects within the tumor microenvironment (TME). Both RANKL and programmed cell death protein 1 (PD-1) inhibitors modulate immune responses, raising concerns about the potential for overactivation of the immune system and increased adverse reactions when used together.We conducted a retrospective analysis to evaluate the safety and efficacy of combined RANKL and PD-1 inhibitor therapy in pa

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… RANKL-expressing tumor cells induce the upregulation of programmed cell death ligand 1 (PD-L1) and immunoglobulin-like transcript 3 on the surface of dendritic cells (DCs), increase the secretion of immunosuppressive cytokines, and downregulate the expression of major histocompatibility complex class …

Antibody-Based Immunotherapeutic Strategies for the Treatment of Hematological Malignancies.

As the most common type of cancer in the world, hematological malignancies (HM) account for 10% of all annual cancer deaths and have attracted more attention. Conventional treatments, such as chemotherapy, radiotherapy, and hematopoietic stem cell transplantation (HSCT), could relieve patients suffering HM. However, serious side effects and high costs bring patients both physical complaints and mental pressure. Recently, compared with conventional therapeutic strategies for HM patients, antibody-based immunotherapies, including cancer vaccines, oncolytic virus therapies, monoclonal antibody tr

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… With a high expression of major histocompatibility complex (MHC)-I/II, costimulatory molecules (ICOS), and adhesion molecule (ICAM), mDCs have powerful antigen-presenting ability, and the antigen is presented to T cell in the T cell area of the lymph nodes, to start the MHC-I-restricted cytotoxic T cell …