Abstract: Chronic inflammatory diseases are becoming a leading cause of death throughout the world. Although such diseases appear to be clinically different, they share many similarities in terms of genetic background and pathophysiological pathways. There is an interest to develop drugs for inhibiting the CD95-mediated non-apoptotic signaling pathway that contributes to inflammation. In particular, neutralizing anti-CD95L monoclonal antibodies are highly desirable. The inventors a neutralizing anti-CD95L monoclonal antibody (mAb), designated JQ3 (IgG1 K). In particular, the neutralizing effect of JQ3 was confirmed since this home-made monoclonal antibody inhibited the CD95-mediated apoptotic signaling pathway induced in T-cell line Jurkat more efficiently than NOK-1 mAb. Interestingly, JQ3 blocked the CD95-mediated Ca2+ response in neutrophils exposed to sera from various inflammatory conditions (COVID 19 patients and anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) patients).

Abstract: The present invention relates the field of reducing CD95-mediated cell motility in a subject, in particular for their use in the reduction of CD-95 mediated cancer cell motility, the reduction of CD95-mediated lymphocyte motility and/or B cell maturation, or the treatment of B-cell tumors, in a subject. The inventors identified a novel family of compounds having the ability to disrupt CD95/PLC?1 interaction and to neutralize the CD95-mediated calcium signaling pathway and cell migration in human peripheral blood lymphocytes (PBLs) and Th17 cells.

Abstract: The present invention relates the field of reducing CD95-mediated cell motility in a subject, in particular for their use in the reduction of CD-95 mediated cancer cell motility, the reduction of CD95-mediated lymphocyte motility and/or B cell maturation, or the treatment of B-cell tumors, in a subject. The inventors identified a novel family of compounds having the ability to disrupt CD95/PLC?1 interaction and to neutralize the CD95-mediated calcium signaling pathway and cell migration in human peripheral blood lymphocytes (PBLs) and Th17 cells.

Abstract: The present invention relates to polypeptides and uses thereof for reducing CD95-meditated cell motility. In particular, the present invention relates to a polypeptide having an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the amino-acid residue at position 175 to the amino-acid residue at position 191 in SEQ ID NO:1.

Abstract: The present invention relates to a method for reducing CD95-mediated cell motility. To identify chemicals disrupting CD95/PLC?1 interaction, the inventors screened a chemical library of EMA/FDA-approved molecules against a protein-fragment complementation assay (PCA) monitoring the binding of CD95 to PLC?1. From this screen, five chemical molecules showed the ability to disrupt CD95/PLC?1 interaction and to neutralize the CD95-mediated calcium signaling pathway and cell migration in human peripheral blood lymphocytes (PBLs) and Th17 cells. Thus, the present invention relates to a method for reducing CD95-mediated cell motility, comprising administering the subject with at least one compound selected from the group consisting of HIV-protease inhibitors (e.g. ritonavir), diflunisal, anethole, rosiglitazone and daunorubicin.

Abstract: The present invention relates to polypeptides and uses thereof for reducing CD95-meditated cell motility.

Abstract: The present invention relates to polypeptides and uses thereof for reducing CD95-meditated cell motility. In particular, the present invention relates to a polypeptide having an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the amino-acid residue at position 175 to the amino-acid residue at position 191 in SEQ ID NO:1.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of Th17-mediated diseases. In particular, the present invention relates to a method of treating a Th17-mediated disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a CD95 antagonist.

Abstract: The present invention relates to methods and pharmaceutical compositions for preventing or reducing metastatic dissemination (i.e. reducing motility of cancer cells). In particular, the present invention relates to a method for preventing or reducing metastatic dissemination (i.e. reducing motility of cancer cells) in a subject suffering from a cancer comprising the steps consisting of i) determining the expression level of at least one biomarker selected from the group consisting of soluble CD95L and EMT promoting factors in a sample obtained from the subject, ii) comparing the expression level determined at step i) with a predetermined reference value and iii) administering the subject with a therapeutically effective amount of C16-ceramide or derivatives such as C16-sphingomyelin and C16-glycosphingolipids when the expression level determined at step i) is higher than the predetermined reference value.

Abstract: The invention relates to new PI3K/AKT/m TOR inhibitors and their use for the prevention and/or the treatment of a disease selected from the group consisting of: inflammatory diseases, autoimmune diseases, neurodegenerative diseases, cancers, transplant rejection, diseases characterized by a premature aging and tuberous sclerosis.

Abstract: The present invention relates to polypeptides and uses thereof for reducing CD95-meditated cell motility. In particular, the present invention relates to a polypeptide having an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the amino-acid residue at position 175 to the amino-acid residue at position 191 in SEQ ID NO:1.

Abstract: The present invention relates to methods and pharmaceutical compositions for preventing or reducing metastatic dissemination (i.e. reducing motility of cancer cells). In particular, the present invention relates to a method for preventing or reducing metastatic dissemination (i.e. reducing motility of cancer cells) in a subject suffering from a cancer comprising the steps consisting of i) determining the expression level of at least one biomarker selected from the group consisting of soluble CD95L and EMT promoting factors in a sample obtained from the subject, ii) comparing the expression level determined at step i) with a predetermined reference value and iii) administering the subject with a therapeutically effective amount of C16-ceramide or derivatives such as C16-sphingomyelin and C16-glycosphingolipids when the expression level determined at step i) is higher than the predetermined reference value.

Abstract: The invention relates to new PI3K/AKT/m TOR inhibitors and their use for the prevention and/or the treatment of a disease selected from the group consisting of: inflammatory diseases, autoimmune diseases, neurodegenerative diseases, cancers, transplant rejection, diseases characterized by a premature aging and tuberous sclerosis.

Abstract: In particular the present invention relates to a method for predicting the risk of relapse and distant metastasis in a patient suffering from a triple negative breast cancer comprising the step of i) determining the level of soluble CD95L in a blood sample obtained from the patient ii) comparing the level determined at step i) with a predetermined reference value and iii) concluding that the patient will exhibit an increased risk of relapse and distant metastasis when the level determined at step i) is higher than the predetermined reference value or concluding that the patient will exhibit a decreased risk of relapse and distant metastasis when the level determined at step i) is lower than the predetermined reference value.

Abstract: The present invention concerns a composition for potentiating formation of DISC (Death Inducing Signaling Complex) macro-complex and for inducing apoptotic signal mediated by death receptors in tumour cells comprising a therapeutically effective amount of an active agent selected among a hypocalcemia-inducing agent, a calcium channel inhibitor and a calcium chelator in association with a therapeutically effective amount of an anticancer agent inducing an apoptotic signal via death receptors Fas, TNF-R1, DR4 and/or DR5.