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: Immunoglobulins (Ig) are expressed either on the surface of B cells or as secreted antibodies by plasma cells that represents the final stage of B cell differentiation. The present invention involves the use of antisense oligonucleotides (ASOs) for either reducing the production of the secreted form or either reducing the production of the membrane form. In particular, the inventors show that antisense oligonucleotides masking the secretory polyadenylation signal induce a decrease in the production of the secreted immunoglobulin. Inversely, antisense oligonucleotides masking the membrane polyadenylation signal induce a decrease in the production of the membrane-anchored immunoglobulin. The proof of concept has been obtained using an ASO hybridizing to the polyadenylation signal (PAS) sequence of the transcript encoding the secreted form of IgE. Indeed, the targeting of this PAS sequence induces a drastic decrease in IgE production.

Abstract: The present invention relates to an recombinant nucleic acid molecule comprising an immunoglobulin heavy chain variable region (VH), an immunoglobulin light chain variable region (VL), an immunoglobulin light chain constant region (CL), an immunoglobulin heavy chain constant region (CH) corresponding to the CH1, hinge, CH2 and CHS protein domains encoded by the human pseudo-gamma gene (??), and its uses for therapeutic or diagnostic purposes. The invention further relates to an antibody encoded by said recombinant nucleic acid molecule, and an expression cassette, vector, viral particle, host cell, transgenic organism or pharmaceutical composition comprising said recombinant nucleic acid molecule.

Abstract: The present invention relates to an antibody comprising an immunoglobulin heavy chain variable region (VH), an immunoglobulin light chain variable region (VL), an immunoglobulin light chain constant region (CL), an immunoglobulin heavy chain constant region (CH), and two sequences encoding peptide linkers (PL1 and PL2), wherein VH is fused to VL through PL1 and CL is fused to CH through PL2, and its uses for therapeutic or diagnostic purposes. The invention further relates to a recombinant nucleic acid molecule encoding said antibody, and an expression cassette, vector, viral particle, host cell, transgenic organism or pharmaceutical composition comprising said recombinant nucleic acid molecule.

Abstract: The present invention concerns a treatment of diseases involving B cells, B lymphocytes or plasmocytes. In particular, it concerns an antisense oligonucleotide or a mixture of antisense oligonucleotides capable of inducing exon skipping at the RNA of the immunoglobulin heavy or light chains, for the use of same in the treatment of diseases involving B cells.

Abstract: The present invention concerns a treatment of diseases involving B cells, B lymphocytes or plasmocytes. In particular, it concerns an antisense oligonucleotide or a mixture of antisense oligonucleotides capable of inducing exon skipping at the RNA of the immunoglobulin heavy or light chains, for the use of same in the treatment of diseases involving B cells.