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CAR-T Cell Therapy in the Treatment of Pediatric Non-Hodgkin Lymphoma.

Non-Hodgkin lymphomas (NHL) are a group of cancers that originate in the lymphatic system, especially from progenitor or mature B-cells, T-cells, or natural killer (NK) cells. NHL is the most common hematological malignancy worldwide and also the fourth most frequent type of cancer among pediatric patients. This cancer can occur in children of any age, but it is quite rare under the age of 5 years. In recent decades, available medicines and therapies have significantly improved the prognosis of patients with this cancer. However, some cases of NHL are treatment resistant. For this reason, immu

EU Regulatory Pathways for ATMPs: Standard, Accelerated and Adaptive Pathways to Marketing Authorisation.

Advanced therapy medicinal products (ATMPs) require evaluation by the European Medicines Agency's Committee for Advanced Therapies prior to being placed on the European market, subject to a Marketing Authorisation granted by the European Commission. In common with other medicinal products, various regulatory pathways are available for taking ATMPs through clinical trials to market authorisation, and the regulatory pathway taken will depend on a product's characteristics and the target patient population. With the industry poised to deliver more late-stage clinical and commercial ATMPs for seri

Secondary antibody deficiencies in the modern era: emerging trends, diagnostic pitfalls, and advances in personalised management.

Secondary antibody deficiencies (SADs) are a significant but frequently under-recognised group of acquired immunodeficiencies. They may arise in various clinical settings, including haematological malignancies, immunosuppressive therapies, and protein-losing conditions. SADs are associated with an increased risk of recurrent and severe infections, hospitalisation, and impaired quality of life. Despite this, diagnostic and treatment pathways remain inconsistent across healthcare settings and regions. Recent advances in the use of structured clinical data, including electronic health records and

Виртуальная физиотерапия на основе нейропрофилактики в множестве склероза: протокол для двойного беспорядочного теста с двойным проверочным склерозом на функцию верхней конечности, почту и качество жизни с молекулярной и функциональной оценкой МРТ.

ВВЕДЕНИЕ: У людей с множественным склерозом (pwMS) широко распространено нарушение конечности (UL), а функциональное восстановление UL является ключевой целью реабилитации. Технологические подходы, как и виртуальная реальность, все более перспективны. В то время как большинство VR-клиентов ориентированы на конкретные задачи, наш клинический подход включает в себя принципы нейропрофилактичности "содействия и сдерживания" (NFI). Чтобы продвинуться вперед, мы разработали погруженное VR программное обеспечение, основанное на принципах NFI, которое ориентировано на функцию UL и способность стоять н

Необычная реакция профилей белков HERV-W в множестве склерозов: потенциальные биомаркеры для развития заболеваний.

ВВЕДЕНИЕ: Протеины конверта syncytin-1 и fHERV-W из эндогенной ретровирусной семьи человека "W" (HERV-W) были определены в качестве потенциальных факторов риска при множественном склерозе (MS). Цель этого исследования заключается в оценке как юморальной, так и клеточной иммунной реакции на антигенные пептиды, получаемые из этих белков, в различных клинических формах и фазах МУ. МЕТОДЫ: Косвенный анализ иммуносорбента, связанного с ферментом (ELISA), использовался для измерения ответов на иммуноглобулин G (IgG) syncytin-1env 486-500 и fHERV-Wenv 486-504 Пептиды у пациентов с склерозом. Дискрими

Potential Utility of A Proliferation-Inducing Ligand (APRIL) in Colorectal Cancer.

APRIL (A proliferation-inducing ligand) is a member of the tumor necrosis factor superfamily that is overexpressed in a variety of malignant tumors, including colorectal cancer (CRC). Its key physiological roles include inducing the immunoglobulin switch and ensuring plasmocyte survival. In terms of pathological roles, APRIL antagonism has been identified as a key target in autoimmune diseases and immunoglobulin disorders. As previously demonstrated, several inflammatory processes occur at the site of neoplastic initial stages, and their local symptoms are difficult to detect, particularly in

Daratumumab as Single Agent in Relapsed/Refractory Myeloma Patients: A Retrospective Real-Life Survey.

BackgroundThe anti-CD38 monoclonal antibody daratumumab is approved as a single agent for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who received at least three prior lines of therapy, including proteasome inhibitor and immunomodulatory agent. A retrospective multicentric study was designed to evaluate feasibility, tolerability, and efficacy of daratumumab in monotherapy in RRMM.MethodsThis study included 44 consecutive RRMM patients that underwent daratumumab monotherapy after a median number of four prior therapies (range 2-9). Patients were treated in seven S

Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.

Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound tr

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… These amino acids activate sensor proteins in the cytoplasm such as mTOR, GCN2, and Sestrin (highlighted in green bold font), directly activate the TCR-CD3 complex, or are metabolized further to affect T cell development and survival. … These amino acids activate sensor proteins in the cytoplasm such as mTOR, GCN2, and Sestrin (highlighted in green bold font), directly activate the TCR-CD3 complex, or are metabolized further to affect T cell development and survival. …

CAR-T cells in the treatment of multiple myeloma: an encouraging cell therapy.

Multiple myeloma (MM) is a malignant disease of plasma cells that accounts for approximately 10% of all hematological malignancies and is characterized by a clonal proliferation of malignant plasma cells in the bone marrow. Numerous therapeutic strategies, including proteasome inhibitors, immunomodulators, monoclonal antibodies against CD38 and autologous stem cell transplantation, have prolonged the median survival of MM patients. Nevertheless, almost all MM patients suffer disease relapses due to drug resistance and eventually die from MM or MM-related complications. Chimeric antigen recepto

Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE).

Chimeric antigen receptor (CAR) T cells are a novel class of anti-cancer therapy in which autologous or allogeneic T cells are engineered to express a CAR targeting a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) is approved for the treatment of refractory/relapsed acute lymphoblastic leukemia in children and young adults as well as relapsed/refractory diffuse large B-cell lymphoma, while axicabtagene ciloleucel (Yescarta™) is approved for the treatment of relapsed/refractory high-grade B-cell lymphoma and primary mediastinal B-cell lymphoma. Both agents are genetically engineered a

Contribution of Macrophages and T Cells in Skeletal Metastasis.

Bone is a common site for metastases with a local microenvironment that is highly conducive for tumor establishment and growth. The bone marrow is replete with myeloid and lymphoid linage cells that provide a fertile niche for metastatic cancer cells promoting their survival and growth. Here, we discuss the role of macrophages and T cells in pro- and anti-tumoral mechanisms, their interaction to support cancer cell growth, and their contribution to the development of skeletal metastases. Importantly, immunotherapeutic strategies targeting macrophages and T cells in cancer are also discussed in

Effects of proton therapy on the tumor immune system and clinical implications: A review.

Proton therapy, an emerging radiation therapy technique, has gained significant attention owing to its unique physical properties and biological effects. This review aims to explore the impact of proton therapy on the tumor immune system and of its combination with other therapies. This review outlines the fundamental principles and oncological applications of proton therapy, followed by an analysis of its impact on the immune system-encompassing draining lymph nodes, peripheral blood immune cells, tumor cell immune responses, and the tumor microenvironment. We further discuss current combinat

Does the B7-H3 Immune Checkpoint Have High Potential as a Therapeutic Target?

B7-H3 (CD276), a member of the B7 family of proteins, is known to play a key role in the progression of a number of cancers. This protein is selectively expressed in both tumor cells and immune cells within the tumor microenvironment. Various investigations, including a number of clinical trials, have reported high levels of expression of this protein in cancerous tissues compared to their healthy counterparts. This difference in expression attracted various research efforts to establish whether such a difference can be linked to the therapeutic potential of this molecule. It is worth noting t

Role of Polymorphisms of NKG2D Receptor and Its Ligands in Acute Myeloid Leukemia and Human Stem Cell Transplantation.

Natural killer cells possess key regulatory function in various malignant diseases, including acute myeloid leukemia. NK cell activity is driven by signals received through ligands binding activating or inhibitory receptors. Their activity towards elimination of transformed or virally infected cells can be mediated through MICA, MICB and ULBP ligands binding the activating receptor NKG2D. Given the efficiency of NK cells, potential target cells developed multiple protecting mechanisms to overcome NK cells killing on various levels of biogenesis of NKG2D ligands. Targeted cells can degrade liga

CHI3L1 в Множественном склерозе-от скамьи до клиники.

Множественный склероз (MS) — хроническое демиелинирующее заболевание центральной нервной системы (CNS) с сложным и не вполне понятным этиопатологическим фоном, предусматривающим воспалительные и нейродегенеративные процессы. CHI3L1 был замешан в таких патологических условиях, как воспаление, повреждение и нейродегенерация, и, вероятно, будет играть определенную роль в физиологическом развитии CNS. CHI3L1 производится главным образом макрофагами CNS, микроглией и активированными астроцитами. Структура выражения CHI3L1 при поражениях MS может поддержать важную роль астроцитов в модуляции подстре

Chimeric antigen receptor T-cell therapy for multiple myeloma.

Multiple myeloma (MM) is a malignant plasma cell disorder that remains incurable for most patients, as persistent clonal evolution drives new mutations which confer MM high-risk signatures and resistance to standard care. The past two decades have significantly refashioned the therapeutic options for MM, especially adoptive T cell therapy contributing to impressive response rate and clinical efficacy. Despite great promises achieved from chimeric antigen receptor T-cell (CAR-T) therapy, the poor durability and severe toxicity (cytokine release syndrome and neurotoxicity) are still huge challen

CAR-T Therapies in Solid Tumors: Opportunities and Challenges.

Purpose of reviewThis review will discuss the challenges facing chimeric antigen receptor (CAR)-T cell application for solid tumors and opportunities to overcome these obstacles. In addition, this review will examine therapies that are in development for pediatric solid tumors.Recent findingsThe similar success of CAR-T cell treatment for hematological malignancies has not been observed in solid tumors because of the hostile tumor microenvironment and tumor heterogeneity. Most strategies developed to combat these limitations emphasize combinatorial techniques that still require further testing

Neurologic adverse events of cancer immunotherapy.

Cancer immunotherapy encompasses a wide range of treatment modalities that harness the anti-tumor effects of the immune system and have revolutionized oncological treatment in recent years, with approval for its use in more and more cancers. However, it is not without side effects. Several neurological adverse events have been recognized associated with immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T-cell therapy, the two main classes of cancer immunotherapy. With the increase in the prevalence of oncological diseases and this type of therapy, it is improbable that neu

A Preliminary Investigation towards the Risk Stratification of Allogeneic Stem Cell Recipients with Respect to the Potential for Development of GVHD via Their Pre-Transplant Plasma Lipid and Metabolic Signature.

The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, we investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen (HLA)-matched related or unr

Ageing, autoimmunity and arthritis: senescence of the B cell compartment - implications for humoral immunity.

Immunosenescence is associated with a decline in both T and B lymphocyte function. Although aged individuals have normal numbers of B cells in the periphery and are capable of mounting robust humoral responses, the antibodies produced are generally of lower affinity and are less protective than those produced by young animals. Here we review multiple studies that address the mechanisms that contribute to this decline. Taken together, these studies suggest that age-associated loss of the ability to generate protective humoral immunity results in part from reduced B lymphopoiesis. As the output