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Биотипные антитела в гематологовых злодеях: атакуют фронтлайн.

С тех пор, как Блинатумомаб утвердился в качестве первого биконкретного антитела (BsAb) в лечении рака, эти иммунодуляторные агенты добились значительного успеха в лимфоидных малигнатах. Через десять лет после предварительного одобрения в рентгеновских условиях блинатумомаб стал частью первой линии индуктивной терапии для пациентов с острой лимфоболической лейкемией (B-ALL). Теперь, six Кроме того, БСАБ имеют разрешение УЛХ на обработку лимфомы В-клеток, не относящихся к Ходжкину, и множественной миеломы (ММ), что позволяет добиться высоких показателей ответов в других сценариях. В лимфоме, эп

Therapeutic Advances in Immunotherapies for Hematological Malignancies.

Following the success of immunotherapies such as chimeric antigen receptor transgenic T-cell (CAR-T) therapy, bispecific T-cell engager therapy, and immune checkpoint inhibitors in the treatment of hematologic malignancies, further studies are underway to improve the efficacy of these immunotherapies and to reduce the complications associated with their use in combination with other immune checkpoint inhibitors and conventional chemotherapy. Studies of novel therapeutic strategies such as bispecific (tandem or dual) CAR-T, bispecific killer cell engager, trispecific killer cell engager, and du

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… The signaling domain is the zeta domain of a T-cell receptor/CD3 complex. BiTEs are composed of a VH domain linked to a VL domain via a short, flexible linker. A BiTE is composed of a scFv, whereas DART molecules are synthesized by cross-linking 2 variable fragments. …

Площадь метилирования ДНК клеток цереброспинальной жидкости в множестве склероза: исследование эпигеномной ассоциации.

Множественный склероз (MS) является хроническим воспалительным заболеванием центральной нервной системы, в которой метилация ДНК может увязывать генетические и экологические факторы риска. Methods: Мы профилировали содержание метилации ДНК по всему геному в клетках цереброспиновой жидкости (CSF) у людей с MS (pwMS) и совпадающими контрольными устройствами. Дифференцированные метилированные позиции (DMP) и регионы (DMR) были интегрированы с транскриптомными данными, аннотациями клеточного хроматина Т и анализом путей. Выражение гамма-протокадерина (ПХДГ) было оценено в первичных подмножествах C

Cytokine release syndrome and cancer immunotherapies - historical challenges and promising futures.

Cancer is the leading cause of death worldwide. Cancer immunotherapy involves reinvigorating the patient's own immune system to fight against cancer. While novel approaches like Chimeric Antigen Receptor (CAR) T cells, bispecific T cell engagers, and immune checkpoint inhibitors have shown promising efficacy, Cytokine Release Syndrome (CRS) is a serious adverse effect and remains a major concern. CRS is a phenomenon of immune hyperactivation that results in excessive cytokine secretion, and if left unchecked, it may lead to multi-organ failure and death. Here we review the pathophysiology of C

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… To further refine this approach, Revitope’s Two GATE technology uses two bispecific antibodies with tumor specific protease – each targeting a different tumor associated antigen and a different half domain of the CD3 subunit; i.e. an active anti-CD3 complex is only formed when both halves of anti-CD3 …

A systematic review of the last two decades of NK cell-based clinical trials: state of the art of AML therapy.

BACKGROUND: Acute myeloid leukemia (AML) remains a significant challenge in hematologic oncology, with high relapse rates and limited treatment options. Natural killer (NK) cells, as key effectors of innate immunity, have shown strong anti-leukemic activity, making them promising candidates for immunotherapy. Despite increasing clinical interest, a comprehensive evaluation of NK cell-based therapies in AML is still needed. METHODS: This systematic review follows the PRISMA guidelines to analyze clinical trials evaluating NK cell therapy in AML, either as a standalone treatment or in combinatio

Возвращенная Множественная миелома в гастроинском кишечном тракте с аберрантным выражением CD3: доклад по делу.

В этом докладе описывается редкий случай рецидива множественной миэломы в желудочно-кишечном тракте с аберрантным выражением CD3. При наличии острой почечной недостаточности у пациента были аномальные вычисления томографического сканирования брюшной полости и таза. После этого колоноскопия обнаружила множество полипов и масс. Гистологический анализ биопсии one Из масс обнаружил диффузный атипичный клеточный инфильтрационный процесс с недифференцированной морфологией в субмукозе, который был положительным для CD3, CD4, слабого и переменного CD79a, CD138, BCL2, CMYC, MUM1, виментина и моноклонно

A discrete choice experiment analysis to understand patient preferences for multiple myeloma treatments.

IntroductionMultiple myeloma (MM) is a malignant plasma cell disorder characterized by the clonal expansion of abnormal plasma cells within the bone marrow. The management of relapsed/refractory multiple myeloma (RRMM) represents a significant challenge as the disease relapses or becomes refractory to previous treatments. Recent advances in therapy have expanded RRMM treatment options. This study aimed to gain a deeper understanding of patients' treatment preferences regarding available therapeutic options.MethodsThis study was designed as a non-interventional descriptive cross-sectional study

Дифференциальное воздействие протеина IL4I1 на лимфоциты от здоровых и многоклерозовых пациентов.

Множественный склероз (MS) — хроническое воспалительное заболевание, характеризующееся иммунопосредованным обезвоживанием центральной нервной системы, что приводит к значительному неврологическому дефициту и нарушению функции ремиелинирования. Мы уже обнаружили, что интерлейкин...four спровоцированные one (IL4I1) протеин модифицирует CNS воспаление и усиливает воспоминание в мышах моделей экспериментального обезвоживания. Однако остается неясным, регулирует ли IL4I1 лимфоцитную активность в MS. Чтобы оценить терапевтический потенциал IL4I1 в MS, мы изучили воздействие лечения IL4I1 на лимфоцит

Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial.

PurposeOur preclinical studies showed that the oncolytic reovirus formulation pelareorep (PELA) has significant immunomodulatory anti-myeloma activity. We conducted an investigator-initiated clinical trial to evaluate PELA in combination with dexamethasone (Dex) and bortezomib (BZ) and define the tumor immune microenvironment (TiME) in patients with multiple myeloma treated with this regimen.Patients and methodsPatients with relapsed/refractory multiple myeloma (n = 14) were enrolled in a phase Ib clinical trial (ClinicalTrials.gov: NCT02514382) of three escalating PELA doses administered on D

JCMM Annual Review on Advances in Biotechnology for the Treatment of Haematological Malignancies: A Review of the Latest In-Patient Developments 2024-2025.

Advances in biotechnology are set to revolutionise the treatment of haematological malignancies. Current treatments have limited efficacy due to their high toxicity and poor long-term outcomes, particularly in acute myeloid leukaemia (AML). In 2024-2025, emerging targeted therapies promise improved results with reduced adverse effects. This review is the first of an annual series exploring the latest in-patient developments in several key areas, focusing on mechanisms. We present advances in the use and action of several therapies including epigenetic modulators, protein degraders, apoptotic i

Наномедицина - мощная терапия CAR-T для множественной миеломы: к программируемой, долговременной и точной иммунотерапии.

Множественная миелома (ММ) по-прежнему является трудновыполнимой гематологией. Несмотря на то, что терапия против созревания клеток B (BCMA), ориентированная на химерик антигенный рецептор Т-клектор (CAR-T), существенно углубила клиническую реакцию у пациентов с рецидивом/переносом MM, ее более широкое клиническое применение по-прежнему сдерживается рецидивом после лечения, недостаточной устойчивостью реакции, длительными сроками производства и ограниченной доступностью. Растущие данные свидетельствуют о том, что рецидив после лечения CAR-T в MM происходит не из одного механизма, а из конверге

Multiple myeloma: signaling pathways and targeted therapy.

Multiple myeloma (MM) is the second most common hematological malignancy of plasma cells, characterized by osteolytic bone lesions, anemia, hypercalcemia, renal failure, and the accumulation of malignant plasma cells. The pathogenesis of MM involves the interaction between MM cells and the bone marrow microenvironment through soluble cytokines and cell adhesion molecules, which activate various signaling pathways such as PI3K/AKT/mTOR, RAS/MAPK, JAK/STAT, Wnt/β-catenin, and NF-κB pathways. Aberrant activation of these pathways contributes to the proliferation, survival, migration, and drug res

Efficacy and safety of approved cellular therapies and bispecific antibodies in solid tumors: the current state.

Cancer immunotherapy is a broad term including naked antibodies, bispecific antibodies (BsAbs), immune-checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell (CAR-T) therapy, cancer vaccines, activated immune cells, and allogeneic hematopoietic cell transplantation. Recent advances in immune-engaging T-cell therapies have led to significant progress in novel treatments across various cancer types, resulting in prolonged patient survival, mainly in patients with hematologic malignancies. Several CAR T-cell constructs and BsAbs have been approved by regulatory authorities worldwide for r

T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors.

T-cell receptor (TCR)-based adoptive therapy employs genetically modified lymphocytes that are directed against specific tumor markers. This therapeutic modality requires a structured and integrated process that involves patient screening (e.g., for HLA-A*02:01 and specific tumor targets), leukapheresis, generation of transduced TCR product, lymphodepletion, and infusion of the TCR-based adoptive therapy. In this review, we summarize the current technology and early clinical development of TCR-based therapy in patients with solid tumors. The challenges of TCR-based therapy include those associ

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… The introduction of new α- and β-TCR proteins, without the silencing of expression of the endogenous α- and β-TCR proteins, could disrupt the stoichiometry required for efficient assembly of an active TCR-CD3 complex. … Molecular architecture of the alphabeta T cell receptor-CD3 complex. Proc Natl Acad Sci USA. 2014;111:17576–17581. doi: 10.1073/pnas.1420936111. 5. Hewitt EW. The MHC class I antigen presentation pathway: strategies for viral immune evasion. …

Клинические и параклинические характеристики отличают усталость от депрессивных фенотипов при множественном склерозе.

В клинической практике, возможно, трудно провести различие между усталостью и депрессией при мультипликационном склерозе (MS). Мы провели два независимых исследования когортных наблюдений, в ходе которых клинические и параклинические особенности отличают пациентов, сообщающих об усталости, но никаких депрессивных симптомов от лиц, страдающих депрессивными симптомами, но не имеющих соответствующей усталости. В исследовании 1 n = 156 пациентов, страдающих от усталости, депрессии, когнитивного обследования и цитометрических измерений потока. В исследовании 2, n = 54 пациента MS провели всеобъемлю

Emerging Immunotherapy for Acute Myeloid Leukemia.

Several immune checkpoint molecules and immune targets in leukemic cells have been investigated. Recent studies have suggested the potential clinical benefits of immuno-oncology (IO) therapy against acute myeloid leukemia (AML), especially targeting CD33, CD123, and CLL-1, as well as immune checkpoint inhibitors (e.g., anti-PD (programmed cell death)-1 and anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) antibodies) with or without conventional chemotherapy. Early-phase clinical trials of chimeric antigen receptor (CAR)-T or natural killer (NK) cells for relapsed/refractory AML showed

CD123 as a Therapeutic Target in the Treatment of Hematological Malignancies.

The interleukin-3 receptor alpha chain (IL-3R), more commonly referred to as CD123, is widely overexpressed in various hematological malignancies, including acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia, hairy cell leukemia, Hodgkin lymphoma and particularly, blastic plasmacytoid dendritic neoplasm (BPDCN). Importantly, CD123 is expressed at both the level of leukemic stem cells (LSCs) and more differentiated leukemic blasts, which makes CD123 an attractive therapeutic target. Various agents have been developed as drugs able to target CD123 on malignant leukemic cells and o

From Molecular Precision to Clinical Practice: A Comprehensive Review of Bispecific and Trispecific Antibodies in Hematologic Malignancies.

Multispecific antibodies have redefined the immunotherapeutic landscape in hematologic malignancies. Bispecific antibodies (BsAbs), which redirect cytotoxic T cells toward malignant targets via dual antigen engagement, are now established components of treatment for diseases such as acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and multiple myeloma (MM). Clinical trials of agents like blinatumomab, glofitamab, mosunetuzumab, and teclistamab have demonstrated deep and durable responses in heavily pretreated populations. Trispecific antibodi

Next-generation antibody-based therapeutics in cancer: antibody-drug conjugates bispecific antibodies across hematologic malignancies and solid tumors.

The therapeutic paradigm in oncology is undergoing a profound transformation driven by antibody-drug conjugates (ADCs) and bispecific antibodies (bsAbs). This review comprehensively summarizes recent clinical advances of these platforms across both hematologic malignancies and solid tumors. ADCs such as trastuzumab deruxtecan have expanded the concept of targetable HER2 expression, demonstrating meaningful intracranial activity and redefining standards of care in HER2-low breast cancer and beyond. The landscape continues to broaden with novel ADC targets (TROP2, CLDN18.2, B7-H3, HER3) and bisp

Targeted immunotherapy: harnessing the immune system to battle multiple myeloma.

Multiple myeloma (MM) remains an incurable hematological malignancy disease characterized by the progressive dysfunction of the patient's immune system. In this context, immunotherapy for MM has emerged as a prominent area of research in recent years. Various targeted immunotherapy strategies, such as monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor T cells/natural killer (NK) cells, and checkpoint inhibitors have been developed for MM. This review aims to discuss promising experimental and clinical evidence as well as the mechanisms of action u