Preclinical evaluation of antigen-sensitive B7-H3-targeting nanobody-based CAR-T cells in glioblastoma cautions for on-target, off-tumor toxicity.

Background: Glioblastoma is the most common lethal primary brain tumor, urging evaluation of new treatment options. Chimeric antigen receptor (CAR)-T cells targeting B7 homolog 3 (B7-H3) are promising because of the overexpression of B7-H3 on glioblastoma cells but not on healthy brain tissue. Nanobody-based (nano)CARs are gaining increasing attention as promising alternatives to classical single-chain variable fragment-based (scFv)CARs, because of their single-domain nature and low immunogenicity.

A single-cell transcriptomic map of the murine and human multiple myeloma immune microenvironment across disease stages.

Background: The long-term effectiveness of immunotherapies against Multiple Myeloma (MM) remains elusive, demonstrated by the inevitable relapse in patients. This underscores the urgent need for an in-depth analysis of the MM tumor-immune microenvironment (TME). Hereto, a representative immunocompetent MM mouse model can offer a valuable approach to study the dynamic changes within the MM-TME and to uncover potential resistance mechanisms hampering effective and durable therapeutic strategies in MM.

AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies.

Until recently, treatment options for patients diagnosed with Acute Myeloid Leukemia (AML) were limited and predominantly relied on various combinations, dosages, or schedules of traditional chemotherapeutic agents. Patients with advanced age, relapsed/refractory disease or comorbidities were often left without effective treatment options. Novel advances in the understanding of leukemogenesis at the molecular and genetic levels, alongside recent progress in drug development, have resulted in the emergence of novel therapeutic agents and strategies for AML patients.

Successful Treatment of Very Severe Sinusoidal Obstruction Syndrome After Gemtuzumab Ozogamicin With Transjugular Intrahepatic Portosystemic Shunt, Defibrotide, and High-Dose Corticosteroids: A Case Report.

Sinusoidal obstruction syndrome (SOS) is a rare but potentially life-threatening complication, usually described in the setting of hematopoietic stem cell transplantation (HSCT). The very severe forms have a high mortality rate (>80%) and need fast recognition and urgent treatment. In this case report, we describe a unique and successful treatment strategy.

The crosstalk between lung cancer and the bone marrow niche fuels emergency myelopoiesis.

Modest response rates to immunotherapy observed in advanced lung cancer patients underscore the need to identify reliable biomarkers and targets, enhancing both treatment decision-making and efficacy. Factors such as PD-L1 expression, tumor mutation burden, and a 'hot' tumor microenvironment with heightened effector T cell infiltration have consistently been associated with positive responses. In contrast, the predictive role of the abundantly present tumor-infiltrating myeloid cell (TIMs) fraction remains somewhat uncertain, partly explained by their towering variety in terms of ontogeny, phenotype, location, and function.

Prolonged Responses in Central Nervous System Relapsed Diffuse Large B-Cell Lymphoma After Chimeric Antigen Receptor T-Cell Therapy Using Targeted Treatments.

The introduction of chimeric antigen receptor T-cell (CAR-T cell) therapy has changed the treatment landscape of diffuse large B-cell lymphoma (DLBCL). However, the optimal treatment strategy after relapse after this therapy still needs to be elucidated. In this report, we describe the case of a 67-year-old male who relapsed after treatment with tisagenlecleucel as a third-line therapy.

Alzheimer's disease linked Aβ42 exerts product feedback inhibition on γ-secretase impairing downstream cell signaling.

Amyloid β (Aβ) peptides accumulating in the brain are proposed to trigger Alzheimer's disease (AD). However, molecular cascades underlying their toxicity are poorly defined. Here, we explored a novel hypothesis for Aβ42 toxicity that arises from its proven affinity for γ-secretases.

Liquid Biopsies as Non-Invasive Tools for Mutation Profiling in Multiple Myeloma: Application Potential, Challenges, and Opportunities.

Over the last decades, the survival of multiple myeloma (MM) patients has considerably improved. However, despite the availability of new treatments, most patients still relapse and become therapy-resistant at some point in the disease evolution. The mutation profile has an impact on MM patients' outcome, while typically evolving over time.

AXL-specific single domain antibodies show diagnostic potential and anti-tumor activity in Acute Myeloid Leukemia.

AXL expression has been identified as a prognostic factor in acute myeloid leukemia (AML) and is detectable in approximately 50% of AML patients. In this study, we developed AXL-specific single domain antibodies (sdAbs), cross-reactive for both mouse and human AXL protein, to non-invasively image and treat AXL-expressing cancer cells. AXL-specific sdAbs were induced by immunizing an alpaca with mouse and human AXL proteins.

γ-Secretase Modulator BPN15606 Reduced Aβ42 and Aβ40 and Countered Alzheimer-Related Pathologies in a Mouse Model of Down Syndrome.

Objectives: Due to increased gene dose for the amyloid precursor protein (APP), elderly adults with Down syndrome (DS) are at a markedly increased risk of Alzheimer's disease (AD), known as DS-AD. How the increased APP gene dose acts and which APP products are responsible for DS-AD is not well understood, thus limiting strategies to target pathogenesis. As one approach to address this question, we used a novel class of γ-secretase modulators that promote γ-site cleavages by the γ-secretase complex, resulting in lower levels of the Aβ42 and Aβ40 peptides.

Listeria monocytogenes Infections in Hematopoietic Cell Transplantation Recipients: Clinical Manifestations and Risk Factors. A Multinational Retrospective Case-Control Study from the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation.

Listeriosis is rare after hematopoietic stem cell transplantation (HCT). Little is known about listeriosis in this population. In this retrospective international case-control study, we evaluated 41 listeriosis episodes occurring between 2000 and 2021 in HCT recipients (111 transplant centers in 30 countries) and assessed risk factors for listeriosis by comparisons with matched controls.

Alzheimer's disease linked Aβ42 exerts product feedback inhibition on γ-secretase impairing downstream cell signaling.

Amyloid β (Aβ) peptides accumulating in the brain are proposed to trigger Alzheimer's disease (AD). However, molecular cascades underlying their toxicity are poorly defined. Here, we explored a novel hypothesis for Aβ42 toxicity that arises from its proven affinity for γ-secretases.

Modeling Alzheimer's disease related phenotypes in the Ts65Dn mouse: impact of age on Aβ, Tau, pTau, NfL, and behavior.

Introduction: People with DS are highly predisposed to Alzheimer's disease (AD) and demonstrate very similar clinical and pathological features. Ts65Dn mice are widely used and serve as the best-characterized animal model of DS.

Methods: We undertook studies to characterize age-related changes for AD-relevant markers linked to Aβ, Tau, and phospho-Tau, axonal structure, inflammation, and behavior.

Disease Perception Is Correlated with Health-Related Quality of Life in Patients Suffering from Myelodysplastic Syndromes: Results of the Belgian Be-QUALMS Study.

Patients with myelodysplastic syndromes suffer from an impaired quality of life that is only partially explained by physical symptoms. In an observational study, we aimed to investigate the impact of current MDS treatments and the influence of disease perception on quality of life. Serial measurement of health-related quality of life was performed by 'the QUALMS', a validated MDS-specific patient reported outcome tool.

Retromer Proteins Reduced in Down Syndrome and the Dp16 Model: Impact of APP Dose and Preclinical Studies of a γ-Secretase Modulator.

Objective: The retromer complex plays an essential role in intracellular endosomal sorting. Deficits in the retromer complex are linked to enhanced Aβ production. The levels of the components of the retromer complex are reported to be downregulated in Alzheimer disease (AD).

Outcome of SARS-CoV2 infection in hematopoietic stem cell transplant recipients for autoimmune diseases.

Hematopoietic stem cell transplant (HSCT) recipients may be at high risk of mortality from coronavirus disease 2019 (COVID-19). However, specific data on COVID-19 after treatment with HSCT in patients affected by autoimmune diseases (ADs) are still lacking. In this multicenter observational study of the European Society for Blood and Marrow Transplantation (EBMT), clinical data on COVID-19 in 11 patients affected by severe ADs treated with HSCT (n = 3 allogeneic transplant; n = 8 autologous transplant) are reported.

Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis.

Introduction: Poor graft function (PGF) is a rare but serious complication of allogeneic hematopoietic cell transplantation (alloHCT). Due to their hematopoietic supporting properties and immune regulatory effects, multipotent mesenchymal stromal cells (MSC) could be considered a good candidate to help to restore bone marrow (BM) niches homeostasis and facilitate hematopoiesis after alloHCT.

Methods: We prospectively assessed the efficacy and safety of ex-vivo expanded BM-derived MSC from third-party donor in a series of 30 patients with prolonged severe cytopenia and PGF after alloHCT.

Reduced synaptic proteins and SNARE complexes in Down syndrome with Alzheimer's disease and the Dp16 mouse Down syndrome model: Impact of APP gene dose.

Introduction: Synaptic failure, a hallmark of Alzheimer's disease (AD), is correlated with reduced levels of synaptic proteins. Though people with Down syndrome (DS) are at markedly increased risk for AD (AD-DS), few studies have addressed synapse dysfunction.

Methods: Synaptic proteins were measured in the frontal cortex of DS, AD-DS, sporadic AD cases, and controls.

Genetic profiling of human bone marrow mesenchymal stromal cells after expansion in clinical grade human platelet lysate.

Mesenchymal stromal cells (MSCs) are non-hematopoietic cells that have a broad therapeutic potential. To obtain sufficient cells for clinical application, they must be expanded . In the initial expansion protocols described, fetal calf serum (FCS) was used as the reference growth supplement, but more recently different groups started to replace FCS with platelet lysate (PL).

Liquid Biopsy-Derived DNA Sources as Tools for Comprehensive Mutation Profiling in Multiple Myeloma: A Comparative Study.

The analysis of bone marrow (BM) samples in multiple myeloma (MM) patients can lead to the underestimation of the genetic heterogeneity within the tumor. Blood-derived liquid biopsies may provide a more comprehensive approach to genetic characterization. However, no thorough comparison between the currently available circulating biomarkers as tools for mutation profiling in MM has been published yet and the use of extracellular vesicle-derived DNA for this purpose in MM has not yet been investigated.

Veno-venous extra-corporeal membrane oxygenation in a COVID-19 patient with cold-agglutinin haemolytic anaemia: A case report.

Overview: The use of extra-corporeal membrane oxygenation (ECMO) therapy to treat severe COVID-19 patients with acute respiratory failure is increasing worldwide. We reported herein the use of veno-venous ECMO in a patient with cold agglutinin haemolytic anaemia (CAHA) who suffered from severe COVID-19 infection.

Description: A 64-year-old man presented to the emergency department (ED) with incremental complaints of dyspnoea and cough since one week.