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Progress in Biological Therapies for Adult-Onset Still's Disease.

Adult-onset Still's disease (AOSD) is a rare multifactorial autoinflammatory disorder of unknown etiology, characterized by an excessive release of cytokines triggered by dysregulated inflammation and articular and systemic manifestations. The clinical spectrum of AOSD ranges from self-limiting forms with mild symptoms to life-threatening cases and presents clinical and biological similarities with the juvenile form (sJIA). Nowadays, the advances in biologic agents no longer limit the treatment to NSAIDs, glucocorticoids, or conventional synthetic DMARDs. The blockade of IL-1 and IL-6 is effec

Aging modulation of the immune system and immunotherapy efficacy in cancer.

Immunosenescence is characterized by immune decline and chronic inflammation. With advancing age, the incidence of tumors increases significantly. Understanding how immunosenescence influences the initiation and progression of tumors, as well as its implications for tumor immunotherapy, has become a matter of urgent importance. This review begins with an analysis of the phenotypic changes and underlying mechanisms associated with immune system and immune cell aging, and further explores the interplay between immunosenescence and tumorigenesis. Evidence indicates that cytokines, cell interactio

Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.

Immune evasion represents a significant challenge in oncology. It allows tumors to evade immune surveillance and destruction, thereby complicating therapeutic interventions and contributing to suboptimal patient outcomes. This review addresses the critical need to understand how cancers evade immune surveillance. It aims to provide a comprehensive overview of strategies of tumors to escape immune detection by examining tumor-induced immune suppression, immune checkpoint regulation, and genetic and epigenetic influences. Moreover, it explores the dynamic role of the tumor microenvironment (TME)

Cytokine Modification of Adoptive Chimeric Antigen Receptor Immunotherapy for Glioblastoma.

Chimeric antigen receptor (CAR) cell-based therapies have demonstrated limited success in solid tumors, including glioblastoma (GBM). GBMs exhibit high heterogeneity and create an immunosuppressive tumor microenvironment (TME). In addition, other challenges exist for CAR therapy, including trafficking and infiltration into the tumor site, proliferation, persistence of CARs once in the tumor, and reduced functionality, such as suboptimal cytokine production. Cytokine modification is of interest, as one can enhance therapy efficacy and minimize off-target toxicity by directly combining CAR thera

Результаты лечения пациентов с множественным склерозом и раком твердых органов ингибиторами иммунной системы.

Множественные склерозы (МС) исключаются из исследований иммунных ингибиторов на контрольно-пропускных пунктах (ИКИ) из-за боязни вспышки MS. Цель этого исследования состоит в том, чтобы сообщить о случаях рецидива НР, связанных с иммунным иммунитетом неблагоприятных явлениях (IRAE) и результатах раковых заболеваний у пациентов НР с твердоорганизованным халатным отношением к КИУ. МЕТОДЫ: В ходе этого ретроспективного исследования были выявлены в электронной форме пациенты, получившие МЦУ в Центре по борьбе с раком в университетских больницах Сейдмана. Была собрана и проанализирована информация

IL-7 по аутоиммунным заболеваниям: механизмы и терапевтический потенциал.

Interleukin-7 (IL-7) — плейотропный цитокин, играющий ключевую роль в развитии, гомеостазисе и функционировании иммунной системы. Растущие данные свидетельствуют о том, что IL-7 связан с патогенезом различных аутоиммунных заболеваний, включая ревматуидный артрит (RA), системный волчан эритематос (SLE), диабет типа 1 (T1D) и множественный склероз (MS). Цель настоящего обзора заключается в обобщении нынешнего понимания роли ИЛ-7 в области аутоиммунных заболеваний с уделением особого внимания ее механизмам действий, последствиям для развития заболеваний и потенциальным видам применения в терапевт

Oncolytic Viruses as Reliable Adjuvants in CAR-T Cell Therapy for Solid Tumors.

Although impactful scientific advancements have recently been made in cancer therapy, there remains an opportunity for future improvements. Immunotherapy is perhaps one of the most cutting-edge categories of therapies demonstrating potential in the clinical setting. Genetically engineered T cells express chimeric antigen receptors (CARs), which can detect signals expressed by the molecules present on the surface of cancer cells, also called tumor-associated antigens (TAAs). Their effectiveness has been extensively demonstrated in hematological cancers; therefore, these results can establish th

Воздействие иммунотерапии рака на рождаемость: уделение особого внимания гематологическим заболеваниям.

В последние годы лечению раковых заболеваний способствовали новые эффективные методы лечения, включая иммунную терапию. Хотя эта терапия повышает показатели выживаемости рака, она может изменять иммунную реакцию и вызывать долгосрочные побочные эффекты, гонадотоксичные последствия и потенциальное воздействие на фертильность мужчин и женщин вызывают все большую озабоченность. Иммунотерапии, такие, как ингибиторы иммунной системы, иммуномодуляторы, моноклонные антитела и CAR-T, могут привести к повышению уровней проинфламмации цитокинов и связанных с иммунным иммунитетом неблагоприятных явлений,

Autoimmune Diseases and Plasma Cells Dyscrasias: Pathogenetic, Molecular and Prognostic Correlations.

Multiple myeloma and monoclonal gammopathy of undetermined significance are plasma cell dyscrasias characterized by monoclonal proliferation of pathological plasma cells with uncontrolled production of immunoglobulins. Autoimmune pathologies are conditions in which T and B lymphocytes develop a tendency to activate towards self-antigens in the absence of exogenous triggers. The aim of our review is to show the possible correlations between the two pathological aspects. Molecular studies have shown how different cytokines that either cause inflammation or control the immune system play a part i

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… It has been suggested that daratumumab may have additional effects such as blocking T cells co-expressing CD38 which are responsible for lupus nephritis and depleting plasmacytoid dendritic cells, also expressing elevated levels of CD38, hence reducing interferon type I activity. …

Case Report: Ofatumumab pourpura - лечение в связи с сопутствующим множественным склерозом и идиопатическим тромбоцитопентом.

В этой связи мы подробно рассказываем о нашем опыте с уникальным пациентом с сопутствующим множественным склерозом (MS) и идиопатическим тромбоцитопеническим пурпурным (ИТП) лечением от атумумаба, что привело к стабильной активности заболеваний и нормализации количества тромбоцитов. ПРЕДСТАВЛЕНИЕ СЛУЧАИ: А 21-year-old Японская женщина имела средний продольный синдром фаскилуса и впоследствии получила диагноз MS. Её лечили метилпреднизолоном (Пульсовая терапия).1,000 мг/сут. 5 днями). Во время ее первой госпитализации количество тромбоцитов было низким.40 × 109/L). На основе исследований, серол

Antibodies to watch in 2018.

The pace of antibody therapeutics development accelerated in 2017, and this faster pace is projected to continue through 2018. Notably, the annual number of antibody therapeutics granted a first approval in either the European Union (EU) or United States (US) reached double-digits (total of 10) for the first time in 2017. The 10 antibodies granted approvals are: brodalumab, dupilumab, sarilumab, guselkumab, benralizumab, ocrelizumab, inotuzumab ozogamicin, avelumab, duvalumab, and emicizumab. Brodalumab, however, had already been approved in Japan in 2016. As of December 1, 2017, nine antibody

Differences between physician and patient preferences for cancer treatments: a systematic review.

BackgroundShared decision-making is useful to facilitate cancer treatment decisions. However, it is difficult to make treatment decisions when physician and patient preferences are different. This review aimed to summarize and compare the preferences for cancer treatments between physicians and patients.MethodsA systematic literature search was conducted on PubMed, Embase, PsycINFO, CINAHL and Scopus. Studies elicited and compared preferences for cancer treatments between physicians and patients were included. Information about the study design and preference measuring attributes or questions

Maintenance therapy in acute myeloid leukemia: advances and controversies.

The last decade has seen steadfast progress in drug development in acute myeloid leukemia (AML) which has moved progressively towards genomic-based therapy. With these advances, outcomes in AML have improved but remains far from satisfactory. One approach towards preventing relapse in AML is to use maintenance therapy in patients, after attaining remission. Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective post-remission therapy that has been proven to reduce the risk of relapse. However, in patients who are ineligible for HSCT or have a high risk of relapse, other effe

Clinical activity of single-dose systemic oncolytic VSV virotherapy in patients with relapsed refractory T-cell lymphoma.

Clinical success with intravenous (IV) oncolytic virotherapy (OV) has to-date been anecdotal. We conducted a phase 1 clinical trial of systemic OV and investigated the mechanisms of action in responding patients. A single IV dose of vesicular stomatitis virus (VSV) interferon-β (IFN-β) with sodium iodide symporter (NIS) was administered to patients with relapsed/refractory hematologic malignancies to determine safety and efficacy across 4 dose levels (DLs). Correlative studies were undertaken to evaluate viremia, virus shedding, virus replication, and immune responses. Fifteen patients receive

Chemokine analysis as a novel diagnostic modality in the early prediction of the outcome of non-union therapy: a matched pair analysis.

BACKGROUND: Despite the regenerative capability of skeletal tissue fracture, non-union is common. Treatment of non-unions remains challenging, and early determination of the outcome is impossible. Chemokines play an important role in promoting the formation of new bone and remodeling existing bone. Despite their importance regarding the regulation of bone biology, the potential of chemokines as biological markers reflecting osseous regeneration is unknown. The purpose of this study was to determine (1) if serum chemokine expression levels correlate with the outcome of non-union surgery and (2)

RNA Therapeutics in Viral Infections and Cancer: Mechanisms, Challenges, and Prospects: A Review.

Background: RNA therapeutics represent a rapidly advancing field with significant potential for treating viral infections and cancer. This review examines the current landscape of RNA-based strategies, including siRNA, miRNA mimics, and antisense oligonucleotides. For viral infections, the focus is on hepatitis B (HBV) and C (HCV), HIV, and SARS-CoV-2. Approaches include targeting viral transcripts directly (e.g., siRNAs against HBV surface antigen) or host factors critical for viral replication (e.g., anti-miR-122 miravirsen for HCV). The successful development of mRNA vaccines for COVID-19 i

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy.

Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening co

Application of toll-like receptors (TLRs) and their agonists in cancer vaccines and immunotherapy.

Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) expressed in various immune cell types and perform multiple purposes and duties involved in the induction of innate and adaptive immunity. Their capability to propagate immunity makes them attractive targets for the expansion of numerous immunotherapeutic approaches targeting cancer. These immunotherapeutic strategies include using TLR ligands/agonists as monotherapy or combined therapeutic strategies. Several TLR agonists have demonstrated significant efficacy in advanced clinical trials. In recent years, multiple reports est

Front line treatment of elderly multiple myeloma in the era of novel agents.

Melphalan combined with prednisone (MP) has long been the historical treatment of reference for a large proportion of elderly myeloma (MM) patients ineligible for autologous stem cell transplantation, and is still the backbone of new regimens that include the new era of novel agents. Melphalan-prednisone-thalidomide (MPT) and melphalan-prednisone-bortezomib (Velcade((R)), MPV), proved superior to MP, currently appear to be the treatments of choice for this population. In the near future melphalan-prednisone-lenalidomide (Revlimid((R)), MPR) will also provide a third therapeutic option (MPT, MP

Несапонин из Панакс Гинсенг поддерживает целостность мозгового барьера, подавляя NF-ИБ и p38 MAP cinase сигнализирующих путей для предотвращения развития экспериментального аутоиммунного энцефаломиэлита.

НЕСАпонинская (NS) фракция является важным активным компонентом Панакс Гинсенга, имеющей многофункциональную фармакологическую деятельность, включая нейрозащиту, иммунную регламентацию, противовоспалительные и антиоксидантные эффекты. Однако воздействие НС на множественный склероз (МС) - хроническое и аутоиммунное демиелионирующее расстройство - пока еще не доказано. Цель настоящего исследования состояла в том, чтобы продемонстрировать фармакологические действия НСУ по дисфункциям движения и соответствующие механизмы действий с использованием экспериментальной аутоиммунной энцефаломиелитной мо