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The application, safety, and future of ex vivo immune cell therapies and prognosis in different malignancies.

IntroductionImmunotherapy has revolutionized how cancer is treated. Many of these immunotherapies rely on ex vivo expansion of immune cells, classically T cells. Still, several immunological obstacles remain, including tumor impermeability by immune cells and the immunosuppressive nature of the tumor microenvironment (TME). Logistically, high costs of treatment and variable clinical responses have also plagued traditional T cell-based immunotherapies.MethodsTo review the existing literature on cellular immunotherapy, the PubMed database was searched for publications using variations of the phr

Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy.

Purpose of reviewAcute myeloid leukemia (AML) in children remains a challenging disease to cure with suboptimal outcomes particularly when compared to the more common lymphoid leukemias. Recent advances in the genetic characterization of AML have enhanced understanding of individualized patient risk, which has also led to the development of new therapeutic strategies. Here, we review key cytogenetic and molecular features of pediatric AML and how new therapies are being used to improve outcomes.Recent findingsRecent studies have revealed an increasing number of mutations, including WT1, CBFA2T

Pooled CAR-T screening in pig-tailed macaques identifies designs with enhanced proliferation, trafficking, and persistence.

AbstractChimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of B-cell malignancies; however, >60% of patients relapse within 1 year, often due to insufficient CAR-T persistence. Although mouse and primary cell models have been instrumental in advancing CAR-T therapy, they frequently fail to predict clinical outcomes, underscoring the need for more translationally relevant models. To address this limitation, we conducted, to our knowledge, the first systematic evaluation of CAR structure-function relationships in an immunocompetent nonhuman primate (NHP) model. We

фазы 1 Исследование талькетамаба, гуманизированного GPRC5D x CD3 bioticle антитела, у японских пациентов с рецидивированными/охотничьими MM.

Биконкретный антителный талькетамаб продемонстрировал значительную реакцию при сильно обработанном рецидиве или рефрактном множественном миеломе (RRMM) в глобальном масштабе фазы 1/2 MonumenTAL-1 Учёба. Это исследование позволило оценить безопасность и эффективность талькетамаба у японских пациентов, предварительно прошедших курс лечения с помощью протеаозного ингибитора, иммунодуляционного препарата, и anti-CD38 Моноклональное антитело. Основными конечными точками являются частота и тип сопутствующих неблагоприятных явлений (ТЕАЭ) и серьезные ПВ, включая токсичность, ограничивающую дозу (ДЛТ)

CAR T-Cells in Multiple Myeloma Are Ready for Prime Time.

The survival of patients with multiple myeloma (MM) has been dramatically improved in the last decade thanks to the incorporation of second-generation proteasome inhibitors (PI), immunomodulatory drugs (IMID), and, more recently, anti-CD38 monoclonal antibodies (MoAb). Nevertheless, still, a major proportion of MM patients will relapse, underscoring the need for new therapies in this disease. Moreover, survival in patients failing the current standard of care regimens (including PI, IMIDs, and anti-CD38 MoAb), which is now defined as triple-class refractory, remains dismal, and new drugs with

33rd Европейский конгресс патологии - резюме.

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The Challenging Approach to Multiple Myeloma: From Disease Diagnosis and Monitoring to Complications Management.

The outcome of multiple myeloma (MM) has significantly improved in the last few decades due to several factors such as new biological discoveries allowing to better stratify disease risk, development of more effective therapies and better management of side effects related to them. However, handling all these aspects requires an interdisciplinary approach involving multiple knowledge and collaboration of different specialists. The hematologist, faced with a patient with MM, must not only choose a treatment according to patient and disease characteristics but must also know when therapy needs t

T-Cell Acute Lymphoblastic Leukemia-Current Concepts in Molecular Biology and Management.

T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon, yet aggressive leukemia that accounts for approximately one-fourth of acute lymphoblastic leukemia (ALL) cases. CDKN2A/CDKN2B and NOTCH1 are the most common mutated genes in T-ALL. Children and young adults are treated with pediatric intensive regimens and have superior outcomes compared to older adults. In children and young adults, Nelarabine added to frontline chemotherapy improves outcomes and end of consolidation measurable residual disease has emerged as the most valuable prognostic marker. While outcomes for de-novo disease are

Chimeric antigen receptor (CAR) immunotherapy: basic principles, current advances, and future prospects in neuro-oncology.

With recent advances, chimeric antigen receptor (CAR) immunotherapy has become a promising modality for patients with refractory cancer diseases. The successful results of CAR T cell therapy in relapsed and refractory B-cell malignancies shifted the paradigm of cancer immunotherapy by awakening the scientific, clinical, and commercial interest in translating this technology for the treatment of solid cancers. This review elaborates on fundamental principles of CAR T cell therapy (development of CAR construct, challenges of CAR T cell therapy) and its application on solid tumors as well as CAR

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… The optimal antigen response of chimeric antigen receptors harboring the CD3zeta transmembrane domain is dependent upon incorporation of the receptor into the endogenous TCR/CD3 complex. J Immunol. 2010;184:6938–6949. doi: 10.4049/jimmunol.0901766. 66. Brocker T. …

Селинксор в сочетании с помалидомидом и дексаметазоном для лечения первичной плазменной лейкемии с 1q21+ аномалией: отчет о деле.

RATALE: Первичная плазменная лейкемия клеток представляет собой редкое и крайне агрессивное нарушение системы крови с быстрым распространением заболеваний и высоким коэффициентом ранней смертности. В настоящее время не существует признанного терапевтического режима, что приводит к принятию стратегий, обычно используемых в отношении множественной миэломы, которая, однако, демонстрирует ограниченную эффективность. Селинксор считается эффективным средством лечения рецидива/рефрактора множественной миеломы, однако в настоящее время нет сообщений о его применении в первичном лейкемии клеток плазмы.

Toxic Epidermal Necrolysis Mimicking Severe Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation: A Diagnostic Challenge.

Background: Toxic epidermal necrolysis (TEN) is a rare but life-threatening complication that may occur in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in the context of extensive drug exposure. In this population, TEN can closely resemble severe acute graft-versus-host disease (GVHD), making diagnosis and management challenging. Case presentation: We report the clinical course of an allo-HSCT recipient who developed a rapidly progressive skin rash early after transplantation, and we analyzed the clinical features, histopathology, treatment and ou

Anti-CD38 monoclonal antibody CM313 for systemic lupus erythematosus: a randomized, double-blind, placebo-controlled phase Ib/IIa trial.

CD38 is highly expressed on various immune cells, including long-lived plasma cells, making it a potential therapeutic target in autoimmune diseases. This phase Ib/IIa study aimed to explore the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of CM313, an anti-CD38 antibody, in patients with systemic lupus erythematosus (SLE). Eligible patients were sequentially enrolled in four ascending dose groups (2, 4, 8, and 16 mg/kg) and randomized 4:1 to receive CM313 or placebo intravenously at days 1, 29, 36, 43, and 50. The primary endpoint was safety, and efficacy was explorato

Безопасность и эффективность дироксимеля фумарата в повторной форме множественного склероза: систематический обзор и метаанализ.

ЦЕЛЬ: Оценка безопасности и эффективности Diroximel Fumarate (DRF) у пациентов с различными формами восстановления MS (RMS) на основе систематического обзора и метаанализа. МЕТОДЫ: Был проведен систематический обзор и метаанализ в соответствии с руководящими принципами ПРИСМА. Базы данных < < Скопус > > , < < Пубмед > > и < < Кокран > > CNTRAL были подвергнуты обыску до декабря 6, 2024, для клинических испытаний и наблюдений за ДРР в РСМ. К числу критериев приемлемости относятся исследования, посвященные оценке безопасности или эффективности ОРР, за исключен

Blast Transformation of Chronic Myeloid Leukemia Driven by Acquisition of t(8;21)(q22;q22)/RUNX1::RUNX1T1: Selecting Optimal Treatment Based on Clinical and Molecular Findings.

The advent of tyrosine kinase inhibitors (TKIs) has changed the natural history of chronic myeloid leukemia (CML), and the transformation from the chronic phase to the blast phase (BP) is currently an uncommon situation. However, it is one of the major remaining challenges in the management of this disease, as it is associated with dismal outcomes. We report the case of a 63-year-old woman with a history of CML with poor response to imatinib who progressed to myeloid BP-CML, driven by the acquisition of t(8;21)(q22;q22)/RUNX1::RUNX1T1. The patient received intensive chemotherapy and dasatinib,

Экулизумаб для связанной с АТКР тромботической микроангиопатии в китайском реципиенте трансплантации почек с типом 2 диабет: отчет по делу.

ЦЕЛЬ: Данное исследование было направлено на изучение эффективности экулизумаба в лечении недавно разработанной тромботической микроангиопатии (TMA), связанной с острым отторжением с помощью Т-клеток (ATCR) у пациентов с типом 2 диабет после трансплантации почек. МЕТОДЫ: Новая тромботическая микроангиопатия после трансплантации почек является относительно редким, но серьезным осложнением, которое клинически трудно уладить и требует своевременного вмешательства для предотвращения пересадки или ранней потери трансплантатата. В настоящее время в клинической практике отсутствует консенсус в отноше

Antibodies to watch in 2020.

This 2020 installment of the annual 'Antibodies to Watch' series documents the antibody therapeutics approved in 2019 and in regulatory review in the United States or European Union, as well as those in late-stage clinical studies, as of November 2019*. At this time, a total of 5 novel antibody therapeutics (romosozumab, risankizumab, polatuzumab vedotin, brolucizumab, and crizanlizumab) had been granted a first approval in either the US or EU, and marketing applications for 13 novel antibody therapeutics (eptinezumab, teprotumumab, enfortumab vedotin, isatuximab, [fam-]trastuzumab deruxtecan,

Multiple myeloma: the (r)evolution of current therapy and a glance into future.

Over the past 20 years, the regulatory approval of several novel agents to treat multiple myeloma (MM) has prolonged median patient survival from 3 to 8-10 years. Increased understanding of MM biology has translated to advances in diagnosis, prognosis, and response assessment, as well as informed the development of targeted and immune agents. Here we provide an overview of the recent progress in MM, and highlight research areas of greatest promise to further improve patient outcome in the future.

Mucosal-Associated Invariant T Cells in Health and Disease.

Mucosal-associated invariant T (MAIT) cells are a population of evolutionarily conserved, unconventional innate-like T lymphocytes that are restricted by major histocompatibility complex Class I-related (MR1) molecules. They can be activated either in a T-cell receptor-MR1- or cytokine-dependent manner. Activated MAIT cells play crucial roles in maintaining homeostasis and the fine regulation of the immune system. This review presents a systematic exploration of the development, biological characteristics, and multiple effects of MAIT cells in health and various diseases. In healthy individual

CAR T cells: engineered immune cells to treat brain cancers and beyond.

Malignant brain tumors rank among the most challenging type of malignancies to manage. The current treatment protocol commonly entails surgery followed by radiotherapy and/or chemotherapy, however, the median patient survival rate is poor. Recent developments in immunotherapy for a variety of tumor types spark optimism that immunological strategies may help patients with brain cancer. Chimeric antigen receptor (CAR) T cells exploit the tumor-targeting specificity of antibodies or receptor ligands to direct the cytolytic capacity of T cells. Several molecules have been discovered as potential t

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… CARs mimic the canonical T cell pathway by virtue of the inclusion of either a single-chain variable fragment (ScFv) derived from a monoclonal antibody or a mutated ligand for target binding, one or more co-stimulatory domains, and the ξ chain of the CD3 complex within a single multi-domain receptor …

Unlocking the Potential of Ganoderma lucidum (Curtis): Botanical Overview, Therapeutic Applications, and Nanotechnological Advances.

Background:Ganoderma lucidum (GL), commonly known as the "Lingzhi" or "Reishi" mushroom, has long been recognized for its potential health benefits and medicinal properties in traditional Chinese medicine. The unique potential combination of bioactive compounds present in GL, such as triterpenoids, polysaccharides, and peptides, has inspired interest in leveraging their therapeutic potential In recent years, the emerging field of nanotechnology has opened up new possibilities for using the remarkable properties of GL at the nanoscale. Objetive: The main objective of this review is to explore t