Phase 1 Trials of Gatralimab, a Next-Generation Humanized Anti-CD52 Monoclonal Antibody, in Participants with Progressive Multiple Sclerosis.

Introduction: Lymphocyte depletion via anti-CD52 monoclonal antibody (mAb) therapy is an effective treatment strategy for relapsing-remitting multiple sclerosis (MS) but is associated with infusion/injection-associated reactions (IARs) and autoimmune-related adverse events (AEs). Gatralimab is a next-generation humanized anti-CD52 mAb.

Methods: Two first-in-human trials were conducted in participants with progressive MS to assess the pharmacodynamics, pharmacokinetics, and safety of gatralimab administered via subcutaneous (SC) and intravenous (IV) routes, and to determine the effect of different comedication regimes on IARs to SC gatralimab.

Pharmacological interventions enhance virus-free generation of -replaced CAR T cells.

Chimeric antigen receptor (CAR) redirected T cells are potent therapeutic options against hematological malignancies. The current dominant manufacturing approach for CAR T cells depends on retroviral transduction. With the advent of gene editing, insertion of a CD19-CAR into the T cell receptor (TCR) alpha constant () locus using adeno-associated viruses for gene transfer was demonstrated, and these CD19-CAR T cells showed improved functionality over their retrovirally transduced counterparts.

Interleukin 8 in postoperative delirium - Preliminary findings from two studies.

Objective: Studies have suggested that inflammation contributes to the pathogenesis of postoperative delirium, but previous results on the proinflammatory cytokine IL-8 in plasma are contradictory. Additionally, a significant fraction of IL-8 is bound to erythrocytes, but the relevance of whole blood IL-8 in delirium has not been studied. In this work, we analyzed the association of postoperative delirium with levels of unbound IL-8 in plasma and levels of IL-8 in whole blood in patients from two studies which were conducted in our department and have not been presented previously.

Intramuscular and intratendinous placenta-derived mesenchymal stromal-like cell treatment of a chronic quadriceps tendon rupture.

Background: Quadriceps tendon ruptures (QTRs) are rare but debilitating injuries, often associated with chronic metabolic conditions or long-term steroid treatment. While the surgical treatment for acute QTRs is described thoroughly, no common strategy exists for the often frustrating treatment of chronic, reoccurring QTRs. The pro-angiogenic and immunomodulatory properties of placenta-derived adherent mesenchymal stromal-like (PLX-PAD) cells have been described to protect musculoskeletal tissues from inflammation and catabolic cytokine migration, yet little is known about the regenerative potential of PLX-PAD cells in repetitively damaged tendon tissue.

Physostigmine for prevention of postoperative delirium and long-term cognitive dysfunction in liver surgery: A double-blinded randomised controlled trial.

Background: Anecdotally, cholinergic stimulation has been used to treat delirium and reduce cognitive dysfunction.

Objective: The aim of this investigation was to evaluate whether physostigmine reduced the incidence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in patients undergoing liver resection.

Design: This was a double-blind, randomised, placebo-controlled trial.

The intratumoral CXCR3 chemokine system is predictive of chemotherapy response in human bladder cancer.

Chemotherapy has direct toxic effects on cancer cells; however, long-term cancer control and complete remission are likely to involve CD8 T cell immune responses. To study the role of CD8 T cell infiltration in the success of chemotherapy, we examined patients with muscle invasive bladder cancer (MIBC) who were categorized on the basis of the response to neoadjuvant chemotherapy (NAC). We identified the intratumoral CXCR3 chemokine system (ligands and receptor splice variants) as a critical component for tumor eradication upon NAC in MIBC.

High prevalence of Streptococcus pyogenes Cas9-reactive T cells within the adult human population.

The discovery of the highly efficient site-specific nuclease system CRISPR-Cas9 from Streptococcus pyogenes has galvanized the field of gene therapy. The immunogenicity of Cas9 nuclease has been demonstrated in mice. Preexisting immunity against therapeutic gene vectors or their cargo can decrease the efficacy of a potentially curative treatment and may pose significant safety issues.

Indomethacin promotes survival of new neurons in the adult murine hippocampus accompanied by anti-inflammatory effects following MPTP-induced dopamine depletion.

Background: Parkinson's disease (PD) is characterized by dopaminergic cell loss and inflammation in the substantia nigra (SN) leading to motor deficits but also to hippocampus-associated non-motor symptoms such as spatial learning and memory deficits. The cognitive decline is correlated with impaired adult hippocampal neurogenesis resulting from dopamine deficit and inflammation, represented in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) mouse model of PD. In the inflammatory tissue, cyclooxygenase (COX) is upregulated leading to an ongoing inflammatory process such as prostaglandin-mediated increased cytokine levels.

Adipose-derived human mesenchymal stem cells induce long-term neurogenic and anti-inflammatory effects and improve cognitive but not motor performance in a rat model of Parkinson's disease.

Background: Mesenchymal stem cells (MSC) are easily harvested, and possess anti-inflammatory and trophic properties. Furthermore, MSC promote neuroprotection and neurogenesis, which could greatly benefit neurodegenerative disorders, such as Parkinson's disease.

Methods: MSC were transplanted one week after 6-hydroxydopamine lesioning and effects were evaluated after 6 months.

Miniaturized bronchoscopy enables unilateral investigation, application, and sampling in mice.

Lung diseases, including pneumonia and asthma, are among the most prevalent human disorders, and murine models have been established to investigate their pathobiology and develop novel treatment approaches. Whereas bronchoscopy is valuable for diagnostic and therapeutic procedures in patients, no equivalent for small rodents has been established. Here, we introduce a miniaturized video-bronchoscopy system offering new opportunities in experimental lung research.

Terminally differentiated CD8⁺ T cells negatively affect bone regeneration in humans.

There is growing evidence that adaptive immunity contributes to endogenous regeneration processes: For example, endogenous bone fracture repair is modulated by T cells even in the absence of infection. Because delayed or incomplete fracture healing is associated with poor long-term outcomes and high socioeconomic costs, we investigated the relationship between an individual's immune reactivity and healing outcome. Our study revealed that delayed fracture healing significantly correlated with enhanced levels of terminally differentiated CD8(+) effector memory T (TEMRA) cells (CD3(+)CD8(+)CD11a(++)CD28(-)CD57(+) T cells) in peripheral blood.

Modulation of cytokine release and gene expression by the immunosuppressive domain of gp41 of HIV-1.

The transmembrane envelope protein gp41 of the human immunodeficiency virus HIV-1 plays an important role during infection allowing fusion of the viral and cellular membrane. In addition, there is increasing evidence that gp41 may contribute to the immunodeficiency induced by HIV-1. Recombinant gp41 and a synthetic peptide corresponding to a highly conserved domain in gp41, the immunosuppressive (isu) domain, have been shown to inhibit mitogen-induced activation of human peripheral blood mononuclear cells (PBMCs) and to increase release of IL-6 and IL-10 from these cells.