Rapid Profiling of Protein Complex Reorganization in Perturbed Systems.

Protein complexes constitute the primary functional modules of cellular activity. To respond to perturbations, complexes undergo changes in their abundance, subunit composition, or state of modification. Understanding the function of biological systems requires global strategies to capture this contextual state information.

CAR-T cells targeting IL-1RAP produced in a closed semiautomatic system are ready for the first phase I clinical investigation in humans.

Purpose Of The Study: The use of chimeric antigen receptor (CAR)-T cells has demonstrated excellent results in B-lymphoid malignancies. The Advanced Therapy Medicinal Products (ATMP) status and good manufacturing practice (GMP) of CAR-T cells require particular conditions of production performed in a pharmaceutical establishment. Our team developed a new medical drug candidate for acute myeloid leukemia (AML), a CAR targeting interleukin-1 receptor accessory protein (IL-1RAP) expressed by leukemia stem cells, which will need to be evaluated in a phase I-IIa clinical trial.

Chimeric antigen receptor T-cells targeting IL-1RAP: a promising new cellular immunotherapy to treat acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) remains a very difficult disease to cure due to the persistence of leukemic stem cells (LSCs), which are resistant to different lines of chemotherapy and are the basis of refractory/relapsed (R/R) disease in 80% of patients with AML not receiving allogeneic transplantation.

Methods: In this study, we showed that the interleukin-1 receptor accessory protein (IL-1RAP) protein is overexpressed on the cell surface of LSCs in all subtypes of AML and confirmed it as an interesting and promising target in AML compared with the most common potential AML targets, since it is not expressed by the normal hematopoietic stem cell. After establishing the proof of concept for the efficacy of chimeric antigen receptor (CAR) T-cells targeting IL-1RAP in chronic myeloid leukemia, we hypothesized that third-generation IL-1RAP CAR T-cells could eliminate AML LSCs, where the medical need is not covered.

Droplet digital PCR allows vector copy number assessment and monitoring of experimental CAR T cells in murine xenograft models or approved CD19 CAR T cell-treated patients.

Background: Genetically engineered chimeric antigen receptor (CAR) T lymphocytes are promising therapeutic tools for cancer. Four CAR T cell drugs, including tisagenlecleucel (tisa-cel) and axicabtagene-ciloleucel (axi-cel), all targeting CD19, are currently approved for treating B cell malignancies. Flow cytometry (FC) remains the standard for monitoring CAR T cells using a recombinant biotinylated target protein.

Systems proteomics approaches to study bacterial pathogens: application to Mycobacterium tuberculosis.

Significant developments and improvements in basic and clinical research notwithstanding, infectious diseases still claim at least 13 million lives annually. Classical research approaches have deciphered many molecular mechanisms underlying infection. Today it is increasingly recognized that multiple molecular mechanisms cooperate to constitute a complex system that is used by a given pathogen to interfere with the biochemical processes of the host.

Elucidation of host-pathogen protein-protein interactions to uncover mechanisms of host cell rewiring.

Infectious diseases are the result of molecular cross-talks between hosts and their pathogens. These cross-talks are in part mediated by host-pathogen protein-protein interactions (HP-PPI). HP-PPI play crucial roles in infections, as they may tilt the balance either in favor of the pathogens' spread or their clearance.

[True precocious puberty in non-tumor hydrocephalus. An analysis of 16 cases].

True precocious puberty occurred in 16 children (15 girls and 1 boy) with non tumoral shunted hydrocephalus at a mean age of 6.8 years. They had mild clinical manifestations of precocious puberty, and the other pituitary functions were found to be normal.

[Sports and maxillofacial injuries: etiological and clinical aspects apropos of 46 cases. Preventive measures].

Maxillofacial injuries due to sporting activities represent approximately 10% of all cases of injury admitted to the University Hospital Center, Lyon, France, and more than half of these occur in football or rugby players. The causes of these accidents (blows against another player, the ground, the field equipment or the game accessories) are discussed. Lesions are generally simple in young, fit adults and results of surgical treatment satisfactory, apart from the rare cases of facial disruption.