Результаты поиска

Понимание и решение проблемы сопротивления иммуномодуляционным соединениям IMID в множестве миеломы.

Лекарственные средства иммуномодулирования (ИМИД), включая линалидомид и помалидомид в сочетании с протеаозными ингибиторами, дексаметазоном и антиCD38 моноклональными антителами, играют центральную роль в лечении множественной миеломы (ММ) на новых диагностированных и рецидивированных этапах. Эти методы лечения значительно улучшили результаты лечения пациентов во всем мире, в результате чего IMID стали одной из опор MM-терапии. В настоящее время разрабатывается новое поколение более мощных соединений, называемых лигами-модуляторами цереблиона Е3 (CELMODs), которые могут заменить старые IMID.

Chimeric Antigen Receptors Based on Low Affinity Mutants of FcεRI Re-direct T Cell Specificity to Cells Expressing Membrane IgE.

IgE is the key mediator of allergic responses. Omalizumab, an IgE-specific monoclonal antibody that depletes IgE, is effective for treating severe allergic asthma. The need for frequent administration of the expensive drug, however, limits its applications. Taking advantage of T cell memory, adoptive T cell therapy (ACT) targeting IgE-producing cells has the potential to achieve long-term suppression of IgE and relief of symptoms for severe allergic diseases. The transmembrane form of IgE (mIgE), which is present on all IgE-producing cells, serves as an excellent molecular target for ACT that

Carbohydrate Targets for CAR T Cells in Solid Childhood Cancers.

Application of the CAR targeting strategy in solid tumors is challenged by the need for adequate target antigens. As a consequence of their tissue origin, embryonal cancers can aberrantly express membrane-anchored gangliosides. These are carbohydrate molecules consisting of a glycosphingolipid linked to sialic acids residues. The best-known example is the abundant expression of ganglioside GD2 on the cell surface of neuroblastomas which derive from GD2-positive neuroectoderm. Gangliosides are involved in various cellular functions, including signal transduction, cell proliferation, differentia

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era.

Chronic lymphocytic leukemia is a lymphoproliferative disorder marked by the expansion of monoclonal, mature CD5+CD23+ B cells in peripheral blood, secondary lymphoid tissues, and bone marrow. The disease exhibits significant heterogeneity, with numerous somatic genetic alterations identified in the neoplastic clone, notably mutated TP53 and immunoglobulin heavy chain mutational statuses. Recent studies emphasize the pivotal roles of genetics and patient fragility in treatment decisions. This complexity underscores the need for a personalized approach, tailoring interventions to individual gen

Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies.

Chimeric antigen receptor (CAR)-T cell therapies have been approved by FDA to treat relapsed or refractory hematological malignancies. However, the adverse effects of CAR-T cell therapies are complex and can be challenging to diagnose and treat. In this review, we summarize the major adverse events, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR T-cell associated HLH (carHLH), and discuss their pathophysiology, symptoms, grading, and diagnosis systems, as well as management. In a future outlook, we also provide an overview of

Antibody drug conjugates in the clinic.

Antibody-drug conjugates (ADCs), chemotherapeutic agents conjugated to an antibody to enhance their targeted delivery to tumors, represent a significant advancement in cancer therapy. ADCs combine the precise targeting capabilities of antibodies and the potent cell-killing effects of chemotherapy, allowing for enhanced cytotoxicity to tumors while minimizing damage to healthy tissues. Here, we provide an overview of the current clinical landscape of ADCs, highlighting 11 U.S. Food and Drug Administration (FDA)-approved products and discussing over 500 active clinical trials investigating newer

Ход работы сессии 25th Европейский конгресс педиатрической ремуматологии (ПСР) 2018) Лиссабон, Португалия. 5-8 сентябрь 2018

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CNS Вовлечение нескольких серий дел Myeloma-A и наррутический литературный обзор.

Фон: участие центральной нервной системы (ЦНС) в множественной миеломе (ММ) представляет собой экстрамуллярное проявление заболевания, которое часто является весьма сложным для врачей, поскольку неврологические симптомы могут легко перекликаться с симптомами, связанными с гиперкалкемией, уремией, высокой вязкостью крови или связанной с лечением нейропатией. Цели: Это ретроспективное исследование было проведено в Клиническом институте Фундэни в Бухаресте с целью выявления и систематического анализа ряда клинических случаев, диагностированных внематочным заболеванием. Методы: В период с 2019 по

IgG replacement in multiple myeloma.

T cell engagers (TCE) such as chimeric antigen receptor (CAR) T cell therapy and bispecific antibodies (BiAbs) for the treatment of multiple myeloma (MM) have significantly improved clinical outcomes, but have also raised awareness for ensuing post-treatment secondary immunodeficiency and hypogammaglobulinemia (HG). As patients with MM live longer, recurrent infections become a significant component of therapy-associated morbidity and mortality. Treatment of HG with immunoglobulin G replacement therapy (IgG-RT) has been a mainstay of the primary immunodeficiency (PI) world, and extrapolation t

Relapsed/Refractory Multiple Myeloma: A Review of Available Therapies and Clinical Scenarios Encountered in Myeloma Relapse.

Multiple myeloma remains an incurable disease with the usual disease course requiring induction therapy, autologous stem cell transplantation for eligible patients, and long-term maintenance. Risk stratification tools and cytogenetic alterations help inform individualized therapeutic choices for patients in hopes of achieving long-term remissions with preserved quality of life. Unfortunately, relapses occur at different stages of the course of the disease owing to the biological heterogeneity of the disease. Addressing relapse can be complex and challenging as there are both therapy- and patie

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

Neutrophils unveiled in chronic lymphocytic leukemia.

This review explores neutrophils' roles in chronic lymphocytic leukemia (CLL), highlighting their functions within the immune system. While neutrophils are known for fighting infections, their altered behavior in CLL significantly impacts disease progression. This review notes the reduced phagocytic abilities of neutrophils and the increased formation of neutrophil extracellular traps (NETs) in patients with CLL. It also examines the effects of CLL treatments, including chemotherapy, immunotherapy and targeted therapies, on neutrophils' count and function, stressing the need for improved strat

Совпадение в полном тексте источника
… Splenic peri-MZ neutrophils (also known as B-cell helper neutrophils ( 138 )) expressed BAFF, APRIL, IL-21, and chemokines such as CXCL12 and CXCL13, which induce the immunoglobulin class switching, somatic hypermutation, and activation of MZ B cells ( 133 ). …

Одинокая панкреатическая эксклюзивная плазмоцитома, диагностированная через эндоскопическую ультразвуковую биопсию с тонкой неё - роль эндоскопической диагностики и многодисциплинарного подхода: тематический доклад и обзор литературы.

Фон и клиническая значимость: Первичная поджелудочная экстрамеуллярная плазменная цитома (ЭМП) крайне необычная, на которую приходится менее 0,1% всех поджелудочных масс, и которая является гораздо более редкой, чем вторичное участие основной миеломы. Презентация дела: 69-летний мужчина был найден с одиночной поджелудочной массой. Эндоскопический ультразвуковой (EUS) наводящий тонкую биопсию (FNB) выявил моноклональное плазмоциклическое распространение с молекулярно подтвержденными KRAS (A146V) и BRAF (G469V) мутации. Многодисциплинарная оценка исключила вторичную локализацию, что привело к ок

Bispecific Antibodies for the Management of Relapsed/Refractory Multiple Myeloma.

Bispecific antibodies (BsAbs) are artificially engineered antibodies that can bind simultaneously to the CD3 subunit within the T-cell receptor complex and an antigen on tumor cells, leading to T-cell activation and tumor cell killing. BsAbs against BCMA or GPRC5D have shown impressive clinical activity in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), with some agents having already received regulatory approval after the third (by the European Medicines Agency, EMA) or fourth (by the Food and Drug Administration, FDA) line of therapy; the results of early-phase

Choosing the Right Therapy for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Consideration of Patient-, Disease- and Treatment-Related Factors.

Treatment of relapsed/refractory multiple myeloma (RRMM) is more complex today due to the availability of novel therapeutic options, mostly applied as combination regimens. immunotherapy options have especially increased substantially, likewise the understanding that patient-, disease- and treatment-related factors should be considered at all stages of the disease. RRMM is based on definitions of the international myeloma working group (IMWG) and includes biochemical progression, such as paraprotein increase, or symptomatic relapse with CRAB criteria (hypercalcemia, renal impairment, anemia, b

Диагностика и лечение ИГАН: стероиды, Будесонид, или, возможно, и то, и другое?

Нефропатия Ига (IgAN), наиболее часто встречающаяся в мире первичная гломерулонефрит, характеризуется мезангиальным залежем Ига и различными гистологическими повреждениями, как описано в Оксфордской системе классификации. Несмотря на хорошо описываемыеfour-Гипотеза, все еще существует множество менее или неописываемых механизмов, которые участвуют в болезнетворном патогенезе, например B-клеток, который, как представляется, инициируется различными антигенами в кишечном микробиоте. Диагноз болезни в настоящее время основан на результатах биопсии почек, поскольку чувствительность и специфичность

Fine-Tuning through Generations: Advances in Structure and Production of CAR-T Therapy.

Chimeric antigen receptor (CAR)-T cell therapy is a promising form of immunotherapy that has seen significant advancements in the past few decades. It involves genetically modifying T cells to target cancer cells expressing specific antigens, providing a novel approach to treating various types of cancer. However, the initial success of first-generation CAR-T cells was limited due to inadequate proliferation and undesirable outcomes. Nonetheless, significant progress has been made in CAR-T cell engineering, leading to the development of the latest fifth-generation CAR-T cells that can target m

Towards Novel Gene and Cell Therapy Approaches for Cervical Cancer.

Cervical cancer is one of the most common malignancies in women, and the majority of cases are caused by infection with high-risk human papilloma virus (HPV) subtypes. Despite effective preventative measures, such as vaccinations against HPV, over 300,000 women die world-wide from cervical cancer each year. Once cervical cancer is diagnosed, treatment may consist of radial hysterectomy, or chemotherapy and radiotherapy, or a combination of therapies dependent upon the disease stage. Unfortunately, overall prognosis for patients with metastatic or recurrent disease remains poor. In these cases,

BCMA/CD19 CAR T cell therapy for refractory myasthenia gravis: Proteomic signatures and single-cell transcriptomics of disease flares.

Myasthenia gravis (MG) is an autoimmune disorder characterized by B cell dysfunction. Here, we designed B cell maturation antigen (BCMA)/CD19 chimeric antigen receptor T cell (CAR T cell) therapy for six refractory MGs, demonstrating favorable safety with grade 1 cytokine release syndrome observed. CAR T cell expansion induced profound B cell depletion, a sustained reduction in acetylcholine receptor (AChR) antibody titers, and symptom improvement. Five patients achieved drug-free remission with minimal manifestations by month 6, persisting through the 12-month follow-up despite B cell reconst

T-cell redirecting bispecific and trispecific antibodies in multiple myeloma beyond BCMA.

Purpose of reviewB-cell maturation antigen (BCMA)-directed T-cell immunotherapies, such as chimeric antigen receptor T-cells (CAR T-cells) and bispecific antibodies (BsAbs) have markedly improved the survival of triple-class refractory multiple myeloma (MM). However, the majority of patients still develops disease progression, underlining the need for new agents for these patients.Recent findingsNovel T-cell redirecting BsAbs targeting alternative tumor-associated antigens have shown great promise in heavily pretreated MM, including patients previously exposed to BCMA-directed therapies. This