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Практические рекомендации в отношении инфекционных профилактических мероприятий и вакцинации нескольких пациентов, страдающих миэломой.

Инфекции по-прежнему являются одной из основных причин заболеваемости и смертности во множестве миеломы (ММ), обусловленной взаимосвязью между иммунной дисфункцией, вызванной болезнями, и иммунодепрессией, связанной с лечением. Внедрение протеазных ингибиторов, иммуномодуляционных препаратов, моноклонных антител, биконкретных антител и химеорической антигенной рецепторной терапии Т (CAR-T) заметно улучшило выживание при одновременном изменении ландшафта инфекционных рисков. Различные стратегии обращения ставят под угрозу иммунитет в рамках различных механизмов. Обычная химиотерапия и некоторые

Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016.

Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial

Development of Targeted Alpha Particle Therapy for Solid Tumors.

Targeted alpha-particle therapy (TAT) aims to selectively deliver radionuclides emitting α-particles (cytotoxic payload) to tumors by chelation to monoclonal antibodies, peptides or small molecules that recognize tumor-associated antigens or cell-surface receptors. Because of the high linear energy transfer (LET) and short range of alpha (α) particles in tissue, cancer cells can be significantly damaged while causing minimal toxicity to surrounding healthy cells. Recent clinical studies have demonstrated the remarkable efficacy of TAT in the treatment of metastatic, castration-resistant prosta

CAR-T cell therapy: developments, challenges and expanded applications from cancer to autoimmunity.

Chimeric Antigen Receptor (CAR)-T cell therapy has rapidly emerged as a groundbreaking approach in cancer treatment, particularly for hematologic malignancies. However, the application of CAR-T cell therapy in solid tumors remains challenging. This review summarized the development of CAR-T technologies, emphasized the challenges and solutions in CAR-T cell therapy for solid tumors. Also, key innovations were discussed including specialized CAR-T, combination therapies and the novel use of CAR-Treg, CAR-NK and CAR-M cells. Besides, CAR-based cell therapy have extended its reach beyond oncology

Mechanisms and management of CAR T toxicity.

Chimeric antigen receptor (CAR) T cell therapies have dramatically improved treatment outcomes for patients with relapsed or refractory B-cell acute lymphoblastic leukemia, large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma. Despite unprecedented efficacy, treatment with CAR T cell therapies can cause a multitude of adverse effects which require monitoring and management at specialized centers and contribute to morbidity and non-relapse mortality. Such toxicities include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, neuro

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… This allows the engineered T cells to bind the target antigen in a major histocompatibility complex (MHC)-independent fashion, followed by robust activation and expansion of the CAR T cell population which promotes tumor elimination. ( 1 ) The anti-CD19 CAR T cell therapies tisagenlecleucel (tisa-cel …

34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 2 : National Harbor, MD, USA. 10 November 2019.

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Устроенная ЦАР клеточная терапия: текущее понимание и перспективы на будущее.

Инженерная клеточная терапия химерического антигенного рецептора (CAR) представляет собой значительный прорыв в иммунотерапии, первоначально в раке и в настоящее время распространяется на различные клинические области. Хотя изначально эти платформы разрабатывались для онкологии, они все чаще адаптируются к таким ненасытным условиям, как аутоиммунные расстройства, инфекционные заболевания, фиброз, проблемы старения и трансплантация органов. В настоящем обзоре содержится подробная информация об эволюции и диверсификации методов ЦАР, включая CAR-T, CAR-NK, CA-Macrophages и CAR-NKT, а также о новы

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… These therapies enable the engineering of immune cells to overcome malignant immune evasion by precisely reprogramming them to recognise specific antigens without relying on major histocompatibility complex (MHC) presentation. … CARs are synthetic, modular receptors that direct immune cells to target tumour-specific antigens without depending on major histocompatibility complex (MHC) recognition. …

Current State of Knowledge on Primary Sjögren's Syndrome, an Autoimmune Exocrinopathy.

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune rheumatic disease characterized by lymphoplasmacytic infiltration of the salivary and lacrimal glands, whereby sicca syndrome and/or systemic manifestations are the clinical hallmarks, associated with a particular autoantibody profile. pSS is the most frequent connective tissue disease after rheumatoid arthritis, affecting 0.3-3% of the population. Women are more prone to develop pSS than men, with a sex ratio of 9:1. Considered in the past as innocent collateral passive victims of autoimmunity, the epithelial cells of the saliv

Immunotherapy of Multiple Myeloma: Promise and Challenges.

Whereas the treatment of MM was dependent solely on alkylating agents and corticosteroids during the prior three decades, the landscape of therapeutic measures to treat the disease began to expand enormously early in the current century. The introduction of new classes of small-molecule drugs, such as proteasome blockers (bortezomib and carfilzomib), immunomodulators (lenalidomide and pomalidomide), nuclear export inhibitors (selinexor), and histone deacetylase blockers (panobinostat), as well as the application of autologous stem cell transplantation (ASCT), resulted in a seismic shift in how

Advances and Challenges in Cervical Cancer: From Molecular Mechanisms and Global Epidemiology to Innovative Therapies and Prevention Strategies.

BackgroundIn the global scenario of public health, cervical cancer poses a major threat with high mortality rates, especially in women. New incidence cases and prevalence vary across different regions, as recently shown by GLOBOCAN data. The development of cervical cancer is primarily due to persistent infection by high-risk genotypes of human papillomavirus (HPV), which is a multifaceted process that is influenced by genetic, environmental, and lifestyle factors.PurposeThe goal of this study is to thoroughly investigate cervical cancer, including its etiology, molecular mechanisms, progressio

Genetic architecture of multiple myeloma: From somatic alterations to germline susceptibility and clinical implications.

Multiple myeloma (MM) is best understood as a dynamically evolving genomic ecosystem shaped by inherited susceptibility, early oncogenic events, and continuous selective pressures. We propose an evolutionary genomics framework integrating germline risk, disease initiation, clonal diversification, and therapeutic adaptation into a unified model of MM biology. Polygenic risk burden, rare predisposing variants, and alterations in DNA repair and telomere pathways create a permissive background that influences precursor states and immune interactions. Primary cytogenetic events, particularly immuno

Combination Immunotherapy as a Promising Strategy to Overcome Immunotherapy Resistance: From Emergence to Next-Generation Approaches.

Advances in immunotherapy, particularly with immune checkpoint inhibitors, have improved clinical outcomes in various cancer subtypes; however, resistance often occurs because these treatments rely on single agents and show limited translational success when combined. Therefore, it is necessary to develop immune checkpoint inhibitor-based combination strategies by integrating next-generation immunotherapies and innovative biomarkers. This review highlights the emerging combinatorial approaches that can be tailored to the distinct tumor microenvironment types to overcome resistance to immune ch

The progress of novel strategies on immune-based therapy in relapsed or refractory diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) can be cured with standard front-line immunochemotherapy, whereas nearly 30-40% of patients experience refractory or relapse. For several decades, the standard treatment strategy for fit relapsed/refractory (R/R) DLBCL patients has been high-dose chemotherapy followed by autologous hematopoietic stem cell transplant (auto-SCT). However, the patients who failed in salvage treatment or those ineligible for subsequent auto-SCT have dismal outcomes. Several immune-based therapies have been developed, including monoclonal antibodies, antibody-drug conjugates, b

Advanced Diagnostic Techniques

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Application and Challenges of Chimeric Antigen Receptor T Cell Therapy in Systemic Rheumatic Diseases and Autoimmune Disorders.

Chimeric antigen receptor T (CAR-T) cell therapy, originally developed for hematologic malignancies, has emerged as a transformative candidate for systemic rheumatic diseases and autoimmune disorders (AIDs). Its unique efficacy in refractory AIDs relies on depleting autoreactive B cells and driving antigen-naïve immune reconstitution, achieving durable drug-free remission in early-phase trials. Despite promising clinical and serological responses lasting 2-5 years without long-term immunosuppression, the field faces unmet needs: complex manufacturing, limited tissue penetration, antigen escape

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… CAR‐T cell therapy integrates antibody specificity with T cell cytotoxicity to selectively eliminate pathogenic cells in an major histocompatibility complex (MHC)‐unrestricted manner, involving genetic engineering of T cells to express CARs, in vitro purification, expansion, activation, and patient reinfusion …

Bone marrow microenvironment in myelodysplastic neoplasms: insights into pathogenesis, biomarkers, and therapeutic targets.

Myelodysplastic neoplasms (MDS) represent a heterogeneous group of malignant hematopoietic stem and progenitor cell (HSPC) disorders characterized by cytopenia, ineffective hematopoiesis, as well as the potential to progress to acute myeloid leukemia (AML). The pathogenesis of MDS is influenced by intrinsic factors, such as genetic insults, and extrinsic factors, including altered bone marrow microenvironment (BMM) composition and architecture. BMM is reprogrammed in MDS, initially to prevent the development of the disease but eventually to provide a survival advantage to dysplastic cells. Rec

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… GM-CSF, granulocyte‒macrophage colony‒stimulating factor; GVAX: GM-CSF-transduced tumor cell vaccines; DC: dendritic cell; TAA: tumor-associated antigen; LAA: leukemia-associated antigen; MHC: major histocompatibility complex; CAR: chimeric antigen receptor; FasL: Fas ligand; TRAIL: Tumor necrosis factor …

Tumor-derived systems as novel biomedical tools-turning the enemy into an ally.

Cancer is a complex illness that presents significant challenges in its understanding and treatment. The classic definition, "a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body," fails to convey the intricate interaction between the many entities involved in cancer. Recent advancements in the field of cancer research have shed light on the role played by individual cancer cells and the tumor microenvironment as a whole in tumor development and progression. This breakthrough enables the utilization of the tumor and its components as biological

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… Neoantigens are a subtype of major histocompatibility complex (MHC)-binding peptide originating from cancer-specific mutations [ 210 ]. …

Challenges and strategies in clinical applications of CAR-T therapy for autoimmune diseases.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated substantial efficacy against various hematological malignancies. The remarkable success of CAR-T cell therapy in targeting B-cell malignancies has generated significant interest in its potential application for treating autoimmune diseases (ADs). By engineering T cells to express CARs that specifically recognize B-cell antigens, researchers aim to selectively eliminate or modulate the dysregulated autoimmune responses underlying disease pathology. Early clinical trials targeting the B-cell marker CD19 have shown promising results,

Химерический антигенный рецептор T-клеточная терапия в нейроиммунных болезнях: механистическое обоснование, клинический опыт и проблемы с переводом.

Нейроиммунные заболевания представляют собой разнородную группу расстройств, при которых клетки В, плазменные удары, плазменные клетки, автоантитела и Т клетки поразному влияют на повреждение тканей. Хотя биологика B-клеток улучшила контроль за заболеваниями, некоторые пациенты по-прежнему сталкиваются с реанимацией, рецидивом после лечения или кумулятивной неврологической инвалидностью. Химерическая антигенная рецепторная T-клетка (CAR-T-клетка) является средством достижения более глубокого и потенциально устойчивого истощения определенных патогенных иммунных клеток. Этот описательный обзор в

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… Binding to a surface antigen activates the CAR independently of major histocompatibility complex presentation and initiates immune-synapse formation, cytoskeletal polarization, cytotoxic granule release, death-receptor signaling, and cytokine production ( 32 ). …

A distinct CAR-T cell phenotype mediates therapeutic response at limited doses.

Chimeric antigen receptor (CAR) T-cell therapies are typically administered at high doses to maximize durable clinical responses. However, manufacturing constraints can limit the production of sufficient cells to achieve the intended dose. Although some patients experience durable responses after receiving lower CAR-T cell doses, the mechanisms underlying efficacy at these limited cell numbers remain poorly understood. To address this, we performed deep phenotyping of anti-CD19 CAR-T cell products and their corresponding leukapheresis starting materials from a phase I/II dose-escalation trial.

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… In line with this, major histocompatibility complex (MHC) molecules on monocytes and dendritic cell subsets from low-dose responders were markedly upregulated at both the transcript and protein levels compared to their counterparts from low-dose non-responders (Fig. 5C, F, G ). …