Dual Chimeric Antigen Receptor T Cells Targeting CD38 and SLAMF7 with Independent Signaling Demonstrate Preclinical Efficacy and Safety in Multiple Myeloma.

Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma targeting B-cell maturation antigen (BCMA) induces high overall response rates. However, relapse still occurs and novel strategies for targeting multiple myeloma cells using CAR T-cell therapy are needed. SLAMF7 (also known as CS1) and CD38 on tumor plasma cells represent potential alternative targets for CAR T-cell therapy in multiple myeloma, but their expression on activated T cells and other hematopoietic cells raises concerns about the efficacy and safety of such treatments.

CAR-T cells derived from multiple myeloma patients at diagnosis have improved cytotoxic functions compared to those produced at relapse or following daratumumab treatment.

Chimeric antigen receptor T cells (CAR-T) have provided promising results in multiple myeloma (MM). However, many patients still relapse, pointing toward the need of improving this therapy. Here, we analyzed peripheral blood T cells from MM patients at different stages of the disease and investigated their phenotype and capacity to generate functional CAR-T directed against CS1 or B Cell Maturation antigen.

The Sec61 translocon is a therapeutic vulnerability in multiple myeloma.

Multiple myeloma (MM) is an incurable malignancy characterized by the uncontrolled expansion of plasma cells in the bone marrow. While proteasome inhibitors like bortezomib efficiently halt MM progression, drug resistance inevitably develop, and novel therapeutic approaches are needed. Here, we used a recently discovered Sec61 inhibitor, mycolactone, to assess the interest of disrupting MM proteostasis via protein translocation blockade.

The long non-coding RNA CRNDE regulates growth of multiple myeloma cells via an effect on IL6 signalling.

Multiple myeloma (MM) is a currently incurable malignancy of antibody-secreting plasma cells. Long non-coding RNAs (lncRNAs) have been recognised as an important class of regulatory molecules which are increasingly implicated in tumorigenesis. While recent studies have demonstrated changes in expression of lncRNAs in MM, the functional significance and molecular pathways downstream of these changes remain poorly characterised.

Effect of aging on the availability of amino acids from an immune-enhancing diet (IED) after a surgical stress in rats.

Background & Aims: Dietary amino acid (AA) requirements increase after a surgical stress while the systemic AA availability from the diet decreases with age, due to splanchnic sequestration. While immune-enhancing diets (IEDs) have been recommended for the nutritional management of surgical patients, the systemic bioavailability of their AA supply has not been evaluated in elderly surgical patients. This was determined in surgically-stressed IED-fed aged rats.

Head injury profoundly affects gut microbiota homeostasis: Results of a pilot study.

Objectives: Head injury (HI) induces a hypercatabolic state, dysimmunity, and septic complications that increase morbidity and mortality. Although compromised immune function is usually incriminated in infection occurrence, gut dysbiosis could also be involved in this phenomenon and, to our knowledge, has never been considered. To assess if HI could affect microbiota, we explored the impact of HI on intestinal microbiota in a rodent model of fluid percussion.

Age-Associated Decrease of the Histone Methyltransferase SUV39H1 in HSC Perturbs Heterochromatin and B Lymphoid Differentiation.

The capacity of hematopoietic stem cells (HSC) to generate B lymphocytes declines with age, contributing to impaired immune function in the elderly. Here we show that the histone methyltransferase SUV39H1 plays an important role in human B lymphoid differentiation and that expression of SUV39H1 decreases with age in both human and mouse HSC, leading to a global reduction in H3K9 trimethylation and perturbed heterochromatin function. Further, we demonstrate that SUV39H1 is a target of microRNA miR-125b, a known regulator of HSC function, and that expression of miR-125b increases with age in human HSC.

Evaluation of a new concept of immune-enhancing diet in a model of head-injured rat with infectious complications: A proof of concept study.

Immune-enhancing diet (IED) utilization in critically ill septic patients is still debated. A new concept of IED has been proposed combining extra glutamine sequentially with either antioxidants or other amino acids, in order to match patient requirements according to their response to injury. We evaluated whether this new IED elicits a more favorable response to stress when compared with two existing IEDs both enriched in arginine but with different levels of anti-oxidants, in a validated rat model combining head injury (HI) and infectious complications.

Impact of qualitative and quantitative variations in nitrogen supply on catch-up growth in food-deprived-refed young rats.

Background: Optimization of the refeeding strategy for the management of malnutrition in early life may enable to improve the quality of catch-up growth. While some data suggest better assimilation of peptides rather than whole proteins the evidence are scarce.

Objective: To compare the nutritional properties of peptides, partially hydrolyzed proteins or whole proteins in food-deprived/refed young rats.

Effect of citrulline on muscle functions during moderate dietary restriction in healthy adult rats.

Low calorie diets are designed to reduce body weight and fat mass, but they also lead to a detrimental loss of lean body mass, which is an important problem for overweight people trying to lose weight. In this context, a specific dietary intervention that preserves muscle mass in people following a slimming regime would be of great benefit. Leucine (LEU) and Citrulline (CIT) are known to stimulate muscle protein synthesis (MPS) in post-prandial and post-absorptive state, respectively.

[Biofilms and public health].

Micro-organisms do not always exist in planctonic forms (single cells or small groups). To survive, especially in limiting media, they may adhere to inert or living surfaces. This enables them to multiply within a community protected by an extracellular matrix, thus forming a biofilm which protects them from antimicrobials.

Arginine reduces bacterial invasion in rats with head injury: an in vivo evaluation by bioluminescence.

Objectives: The benefit of arginine in intensive care unit patients with severe sepsis is still controversial. An excessive supply of arginine could lead to an overproduction of nitric oxide and could be responsible for septic shock and multiorgan failure. However, this claim is not supported by any experimental or clinical data.

In vivo bioluminescent imaging of a new model of infectious complications in head-injury rats.

Infectious complications are responsible for 10-25% of mortality in head-injured patients. In the present work we developed a model of infectious complications in head-injury rats using Escherichia coli (E. coli) with a stable copy of the lux operon, and monitored the infection in vivo by optical imaging.

TPL-2-mediated activation of MAPK downstream of TLR4 signaling is coupled to arginine availability.

The innate immune response is influenced by the nutrient status of the host. Mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase 1 (ERK1) and ERK2, are activated after the stimulation of macrophages with bacterial lipopolysaccharide (LPS) and are necessary for the optimal production of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). We uncovered a role for the extracellular nutrient arginine in the activation of ERK1/2 in LPS-stimulated macrophages.

[Compared viability of planctonic bacteria and bacteria in biofilms by flow cytometry].

Study of biofilms adhering to various surfaces shows the presence of several layers of cells. A small percentage can grow immediately. Are the others viable? These cells are in a resting phase and exhibit a metabolic gradient through the depth of the biofilm.

Evaluation of biohazards in dehydrated biofilms on foodstuff packaging.

Plastic materials used for food packaging are clean but not sterile when the food is just packaged. Accidental wet contamination may occur at every moment between packaging and opening by the consumer: on polyethylene (PET), bacteria may adhere strongly and constitute a biofilm in less than 24 h. By rolling on themselves, PET sheets may contaminate food.

[Infection on foreign material: bacterial colonization of ureteral endoprostheses].

Infection on foreign body: bacterial colonization of ureteric stents. The most frequent cause of the early removal of ureteric endoprostheses (double J) is generally due to bacterial colonization. In order to prevent or to restrict the prosthesis colonization, it is necessary to understand the major steps and the factors influencing the colonization.

The role of p53 as a transcription factor in the induction of apoptosis.

The tumor suppressor gene p53 plays a major role in the protection of cells from DNA damage. Activation of the protein in response to irradiation or genotoxic agents, and possibly by other signals, results in growth arrest at the G1 phase of the cell cycle or in apoptosis. While it has been shown that the ability of p53 to function as a sequence-specific transcriptional activator is necessary for the induction of growth arrest, the mechanism of p53-mediated apoptosis is not clear yet.

Microorganisms as a tool of studying copper metal ions--induced changes in electrophysical cell properties.

Microorganisms are very sensitive to the effect of metal ions and a deficit or an excess of essential metal ions may induce some cell disturbances. The main objective of this research is to evaluate the effect of toxic metal ions. Doing that, the effects of metal ions on the electrophysical properties of the cell membrane, probed by electroorientational spectroscopic techniques and analysis of the electrophoretic mobility of cells have been chosen for investigation.

[In vivo and in vitro analysis of the ability of urinary catheter to microbial colonization].

Bacterial adhesion to biomaterials is a complex phenomenon involving numerous factors. The ability to reduce urinary catheters infections simply by general hygiene and asepsis is low: an ascending colonization cannot be avoided. This will lead to a clinical infection only if several factors favour the bacterial adhesion or the bacterial coaggregation and the feeding of the bacterial biofilm.

[Prevention of cariogenic dental plaque. Study of the structures implicated in the adhesion and coaggregation in Streptococcus mutans and Streptococcus sobrinus].

Cariogenic dental plaque may be assimilated to a biofilm resulting from the adhesion of S. mutans, then from the coaggregation of other streptococci, or other genus. We used a static monospecific biofilm model.

FT-IR spectroscopy study of perturbations induced by antibiotic on bacteria (Escherichia coli).

Fourier transform infrared spectroscopy (FT-IR) is an analysis method which over the spectral absorption, gives information about the molecular structures of systems. Recently, this method is widely used to the investigation of complex systems like cells and bacteria. Characteristic of FT-IR spectrum of bacteria depend closely to physiological and culture parameters.

Monitoring of bacterial growth and structural analysis as probed by FT-IR spectroscopy.

Fourier-transform infrared spectroscopy was used to explore structural changes in bacteria under different incubation conditions. In particular, differences between Bradyrhizobium japonicum (BRJ) grown in liquid and on solid media were investigated, as well as the rearrangement of BRJ after transfer from one medium to the other. The FT-IR absorption bands located between 1200 and 900 cm-1 region, vary in spectral shape and intensity when BRJ were suspended in solution medium or plated on solid medium.