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Sestrin-2: a new biomarker for type 2 Diabetes Mellitus and Insulin resistance.

Multiple myeloma (MM) is the second most common haematological malignancy characterised by clonal proliferation of plasma cells within the bone marrow. Despite advances in treatment options, myeloma remains incurable. Relapsed MM poses significant challenges due to clonal evolution, drug resistance, patient comorbidities and therefore complexities of therapeutic decision-making. A critical question in managing relapsed MM is whether to switch drug classes or retreat with agents within the same class. The question is present with the recent addition of three new drug classes (XPO1 inhibitors, B

Evolving therapy of adult acute lymphoblastic leukemia: state-of-the-art treatment and future directions.

Recent years have witnessed major advances that have improved outcome of adults with acute lymphoblastic leukemia (ALL). The emergence of the concept of measurable residual disease has fine-tuned our prognostic models and guided our treatment decisions. The treatment paradigms of ALL have been revolutionized with the advent of tyrosine kinase inhibitors targeting BCR-ABL1, monoclonal antibodies targeting CD20 (rituximab), antibody-drug conjugates targeting CD22 (inotuzumab ozogamicin), bispecific antibodies (blinatumomab), and CD19 chimeric antigen receptor T cell therapy (tisagenlecleucel). T

Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.

The increasing global burden of cancer necessitates innovative therapeutic strategies. Cell therapy represents a major breakthrough in oncology, evolving rapidly from the successful application of chimeric antigen receptor T (CAR-T) cells in hematologic malignancies to a multiplatform landscape characterized by the concurrent development of diverse strategies. Current research focuses on T cell receptor-engineered T (TCR-T) cells, tumor-infiltrating lymphocytes (TILs), gamma delta (γδ) T cells, CAR-natural killer (CAR-NK) cells, CAR-macrophages (CAR-Ms), and various strategies based on dendrit

Seamless Navigation of Bispecific Therapies: Optimizing Management and Outpatient Access With a Focus on Coordination.

Bispecific antibodies (BsAbs) have emerged as crucial therapeutic agents for patients with relapsed/refractory diffuse large B-cell lymphoma, multiple myeloma, and most recently, lung cancer. These therapies have demonstrated remarkable efficacy in clinical trials; however, multidisciplinary collaboration is essential to ensure optimal patient outcomes amid the operational complexities associated with BsAb therapy. As BsAbs are being prepared for broader adoption, clinicians and treatment centers must navigate operational challenges, including financial considerations, patient selection, careg

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,

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… In addition to mAbs, bispecific T cell engagers (BiTEs) comprise an antibody fragment targeting the TCR-CD3 complex and a disease-specific antigen-binding domain, bridging T cells and target cells to induce an artificial immune synapse [ 75 ]. …

Cancer Therapy-Induced Encephalitis.

Encephalitis associated with cancer therapies is a rare but serious complication that can significantly impact patients' quality of life and it requires prompt identification and management. Over the past two decades, immunotherapy-particularly immune checkpoint inhibitors-has become a cornerstone of cancer treatment, with up to half of metastatic cancer patients in economically developed countries now receiving these therapies. The widespread adoption of immunotherapy has led to improved survival rates and long-term remissions, even in patients with advanced metastatic disease. However, as im

Clinical evidence for immune-based strategies in early-line multiple myeloma: current challenges in decision-making for subsequent therapy.

Almost all patients with multiple myeloma (MM) will eventually develop disease that has relapsed with or become refractory to available treatments and will require additional therapy. However, data are still lacking on how best to sequence regimens in the relapsed/refractory (RR) setting after the failure of early-line lenalidomide, bortezomib, and/or daratumumab, the most commonly used agents in clinical practice today. With the treatment landscape rapidly changing in response to emerging clinical trial data and approvals of several new drugs and additional combinations, it is critically impo

Azoximer Bromide: Mystery, Serendipity, and Promise.

Azoximer bromide (AZB) was identified as an immunomodulator, and was initially developed and currently successfully indicated as one of several natural polyelectrolytes, a vaccine adjuvant, and an effective agent for the treatment of infectious and inflammatory diseases of viral, bacterial, and fungal origin. AZB has the potential to increase an individual's resistance to local and general infection and is indicated for the treatment of viral infections, and has also demonstrated clinical efficacy in the treatment of a variety of secondary immunodeficiencies. However, AZB may offer long-term p

Orchestrating an immune response against cancer with engineered immune cells expressing αβTCRs, CARs, and innate immune receptors: an immunological and regulatory challenge.

Over half a century ago, the first allogeneic stem cell transplantation (allo-SCT) initiated cellular immunotherapy. For several decades, little progress was made, and toxicity of allo-SCT remained a major challenge. However, recent breakthroughs have opened new avenues to further develop this modality and to provide less toxic and equally efficient interventions for patients suffering from hematological or solid malignancies. Current novel cellular immune interventions include ex vivo expansion and adoptive transfer of tumor-infiltrating immune cells or administration of drugs which antagoniz

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… Interestingly, introduction of the γδTCR leads to down-regulation of the endogenous TCR, likely due to competition for components of the CD3 complex. …

Effectiveness and safety of teclistamab for relapsed or refractory multiple myeloma: a systematic review and meta-analysis.

BackgroundMultiple myeloma (MM) is a hematological malignancy with limited treatment options for patients with relapsed/refractory MM (RRMM). Teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody, has shown promising results in clinical trials and real-world studies.MethodsPubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library, ClinicalTrials.gov, and meeting libraries were searched from inception to 14 November 2024. The assessed outcomes included overall survival (OS), progression-free survival, time to next treatment, duration of response, overall response rate (ORR),

Lenalidomide in the treatment of anti-myelin-associated glycoprotein neuropathy: A phase 1 study to identify the maximum tolerated dose.

BackgroundAnti-myelin-associated glycoprotein (MAG) neuropathy is a debilitating demyelinating polyneuropathy with no approved therapies. Our primary objective was to ascertain lenalidomide safety and maximum tolerated dose (MTD) in anti-MAG neuropathy.MethodsThis phase 1b, open-label, single-arm, dose-finding trial was conducted from 2019 through 2022. The original design included a dose-escalation/extension phase followed by a dose-expansion phase. Three doses of lenalidomide were evaluated: 10, 15, and 25 mg. The main outcome was the MTD.ResultsEleven patients enrolled (10 men), with a mean

Targeting degradation of IKZF1 and IKZF3 through modulation of the E3 ligase substrates in the context of cellular therapies for multiple myeloma.

Multiple myeloma (MM) is a blood cancer characterized by the clonal evolution of plasma cells. In 2022, there were an estimated 118 000 MM cases and 121 000 deaths worldwide. The treatment landscape of MM has undergone a dramatic transformation in recent decades, shifting from conventional chemotherapy to more targeted approaches. In order to overcome intrinsic and acquired resistance mechanisms that frequently restrict the efficacy of single-agent therapies, drug combination strategies have been developed to simultaneously target multiple pathogenetic pathways. Building on the success of immu

Targeted Delivery Strategies for Multiple Myeloma and Their Adverse Drug Reactions.

Currently, multiple myeloma (MM) is a prevalent hematopoietic system malignancy, known for its insidious onset and unfavorable prognosis. Recently developed chemotherapy drugs for MM have exhibited promising therapeutic outcomes. Nevertheless, to overcome the shortcomings of traditional clinical drug treatment, such as off-target effects, multiple drug resistance, and systemic toxicity, targeted drug delivery systems are optimizing the conventional pharmaceuticals for precise delivery to designated sites at controlled rates, striving for maximal efficacy and safety, presenting a promising appr

Регулярная молекула-а регулирует ответные реакции, связанные с нейтрофильом TH17 в CNS автоиммунитет.

МЯСО И АЙМ: Отталкивающая молекула наведения-А (RGMA) хорошо известна своей ролью в нейро-воспалении и ремонте CNS с помощью Т-образных клеток. Врожденные иммунные взаимодействия, особенно между нейтрофилами и клетками TH17, становятся критическими движущими силами нейроинфламматической патологии в множестве склерозов (MS). Вопрос о том, регулирует ли РГМ эти связанные с нейтрофильом ответы TH17, остается в значительной степени неизвестным. Уточнение этого механизма может выявить новые терапевтические цели для НР. МЕТОДЫ: Уровни сера РГМ, БМП4, нейтрофильная эластаза (NE), IL-17A, и подстрекат

Natural Killer Cells in the Malignant Niche of Multiple Myeloma.

Natural killer (NK) cells represent a subset of CD3- CD7+ CD56+/dim lymphocytes with cytotoxic and suppressor activity against virus-infected cells and cancer cells. The overall potential of NK cells has brought them to the spotlight of targeted immunotherapy in solid and hematological malignancies, including multiple myeloma (MM). Nonetheless, NK cells are subjected to a variety of cancer defense mechanisms, leading to impaired maturation, chemotaxis, target recognition, and killing. This review aims to summarize the available and most current knowledge about cancer-related impairment of NK c

CRISPR-Cas9-Based Gene Knockout of Immune Checkpoints in Expanded NK Cells.

Natural killer (NK) cell immunotherapy has emerged as a novel treatment modality for various cancer types, including leukemia. The modulation of inhibitory signaling pathways in T cells and NK cells has been the subject of extensive investigation in both preclinical and clinical settings in recent years. Nonetheless, further research is imperative to optimize antileukemic activities, especially regarding NK-cell-based immunotherapies. The central scientific question of this study pertains to the potential for boosting cytotoxicity in expanded and activated NK cells through the inhibition of in

Всеобъемлющий анализ перенаселенности клеток В у пациентов с множественным склерозом в результате массовой цитометрии и протеомики.

Ocrelizumab, анти-CD20 антитела, истощает клетки CD20+B, которые впоследствии перенаселяются в течение месяцев. Мало что известно об изменениях в других популяциях иммунных клеток и молекулярных маркерах, связанных с перенаселенностью клеток В. Здесь мы провели всеобъемлющую характеристику иммунных клеток пациентов с множественным склерозом (MS) при помощи массовой цитометрии. Около 50% пациентов показали наивную перенаселенность клеток B через 6 месяцев, главным образом с фенотипом переходного периода, в то время как CD27+ памяти B клетки только редко перенаселялись. Эта перенаселенность была

Multiple Myeloma: The Role of Autologous Stem Cell Transplantation in the Era of Immunotherapy.

Upfront high-dose therapy with melphalan (HDM) followed by autologous stem cell transplantation (ASCT) has established itself as a core treatment for newly diagnosed multiple myeloma (NDMM) patients in the past 30 years. Induction therapy, HDM-ASCT, and subsequent consolidation and maintenance therapy comprise the current fundamental framework for MM treatment. The introduction of anti-CD38 monoclonal antibodies such as daratumumab and isatuximab has changed the treatment paradigm for transplant-eligible NDMM patients in that quadruplets have become the new standard induction therapy. The trea

Mucosal-Associated Invariant T Cells Display Diminished Effector Capacity in Oesophageal Adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is an aggressive malignancy with poor prognosis, and incidence is increasing rapidly in the Western world. Mucosal-associated invariant T (MAIT) cells recognize bacterial metabolites and kill infected cells, yet their role in OAC is unknown. We aimed to elucidate the role of MAIT cells during cancer development by characterizing the frequency, phenotype, and function of MAIT cells in human blood and tissues, from OAC and its pre-malignant inflammatory condition Barrett's oesophagus (BO). Blood and tissues were phenotyped by flow cytometry and conditioned media

The interplay of immunity and growth: a case of combined variable immunodeficiency and growth hormone deficiency.

INTRODUCTION: Common variable immunodeficiency (CVID) is one of the more common immunodeficiencies seen in clinical practice with a complex disease pathology; while growth hormone deficiency (GHD) is a disorder characterized by complete or relative absence of the human growth hormone. CASE PRESENTATION: This case report presents a 13-year-old female patient with a long history of recurrent respiratory tract and ear infections, along with a notable failure to hit her developmental milestones early in the second decade of her life. The diagnosis was based on a thorough investigation of serum im