Abstract: Natural Treg (nTreg) can potentially suppress cell immune response. Consequently, these CD4+ CD25+ CD127low Foxp3+ T cells are used in adoptive therapy against autoimmune and GVH disease. One difficulty is the varying functional properties depending on the microenvironment that may cause the loss of their suppressive activity and promote TH17- induced inflammatory effects. By ex vivo transdetermination of CD31 TH0 cells, the inventors established and expanded a Foxp3 regulatory T cell population (CD31d-Treg cells) functionally committed to exert a permanent Ag-specific regulatory activity whichever the microenvironmental conditions are. By contrast to nTreg cells, CD31d-Treg cells do not express the IL1 Receptor whose activation is required for IL-17 production. Accordingly, the present invention relates to a population of CD31d-Treg cells functionally committed to exert a regulatory activity and their use for Treg-based adoptive therapy.

Abstract: The present invention relates to a method for ex vivo generating and expanding MHCII restricted CD4+ Foxp3+ regulatory T cells, and therapeutic uses thereof. The inventors here demonstrated the optimal conditions for inducing Foxp3 expression in naive CD3+ CD4+ TCR??+ MHCII restricted T following polyclonal or following antigen-specific activation. They also developed an experimental procedure to generate autologous CD8+ T cell lines functionally committed to lyse tumor-antigen specific FOXP3 expressing TCR??+ MHCII restricted T cells, pathogenic CD4+ T cells that favour tumor cell immune evasion. In particular, the present invention relates to a method for generating ex vivo MHCII restricted CD4+ Foxp3+ regulatory T cells having the following phenotype: CD3+ CD4+ Foxp3+.

Abstract: The present invention relates to a method for ex vivo generating and expanding ?? Foxp3+ regulatory T cells, and therapeutic uses thereof. The inventors performed the induction of Foxp3+ expression in ex vivo human induced tumor-antigen specific CD4? TCR?? unrestricted T cells and the induction of autologous CD8-mediated T-cell responses against tumor-antigen specific FOXP3 expressing CD4+ TCR?? unrestricted T cells. The inventors developed a method to ex vivo generated and expanded antigen specific Foxp3 expressing CD3+ TCR??+ unrestricted T cells, committed to exclusively exert regulatory activity, whichever culture condition of stimulation is. In particular, the present invention relates to a method for generating ex vivo ?? Foxp3+ regulatory T cells having the following phenotype: CD3+ TCR??+ Foxp3+.

Abstract: Among regulatory T cells, natural regulatory T cells (nTregs) ensure the control of self-tolerance and are currently tested in clinical trials in autoimmune diseases and allogeneic hematopoietic stem cell transplantation. Here the inventors show that based on CD39/CD26 markers, the human nTreg population is comprised of 5 major cell subsets each representing a distinct state of maturation. Phenotypic and genetic characteristics of the subsets illustrate the structural parental maturation between subsets which further correlates with expression of regulatory factors. Importantly, the inventors also show that blood nTreg CD39/CD26 profile, remaining constant over a 2year period in healthy persons but varying between individuals, represents a novel biomarker for monitoring chronic diseases, as illustrated in their preliminary study on AI (dermatomyositis, rheumatoid arthritis and leukemias).

Abstract: The present invention relates to a method for ex vivo generating and expanding ?? Foxp3+ regulatory T cells, and therapeutic uses thereof. The inventors performed the induction of Foxp3+ expression in ex vivo human induced tumor-antigen specific CD4+ TCR?? unrestricted T cells and the induction of autologous CD8-mediated T-cell responses against tumor-antigen specific FOXP3 expressing CD4+ TCR?? unrestricted T cells. The inventors developed a method to ex vivo generated and expanded antigen specific Foxp3 expressing CD3+ TCR??+ unrestricted T cells, committed to exclusively exert regulatory activity, whichever culture condition of stimulation is. In particular, the present invention relates to a method for generating ex vivo ?? Foxp3+ regulatory T cells having the following phenotype: CD3+ TCR??+ Foxp3+.

Abstract: The present invention relates to therapeutic uses of ex vivo generated Foxp3+ regulatory T cells. The inventors showed the presence of Foxp3+ expressing T cells in tumor infiltrating lymphocytes (TILs) isolated from luminal-B breast cancer. The inventors performed an ex vivo generation and expansion of specific CD3+ TCRy8+ expressing Foxp3: CD3+ TCRy8+ T cells maintain their Foxp3 level and their suppressive activity, after a further 21-day-culture. They also showed that tumor Ag-specific CD3+ TCR Va24+ T cells maintain their ability to perform suppressive function in pro-inflammatory conditions. In particular, the present invention relates to immunotherapeutic uses of at least one of ex vivo generated Foxp3+regulatory T cells population selected among a MHCII restricted CD4+Foxp3+regulatory T cells population, a y8 Foxp3+regulatory T cells population and an invariant Foxp3+regulatory T cells population.

Abstract: The present invention relates to a method for ex vivo generating and expanding MHCII restricted CD4+ Foxp3+ regulatory T cells, and therapeutic uses thereof. The inventors here demonstrated the optimal conditions for inducing Foxp3 expression in naive CD3+ CD4+ TCR??+ MHCII restricted T following polyclonal or following antigen-specific activation. They also developed an experimental procedure to generate autologous CD8+ T cell lines functionally committed to lyse tumor-antigen specific FOXP3 expressing TCR??+ MHCII restricted T cells, pathogenic CD4+ T cells that favour tumor cell immune evasion. In particular, the present invention relates to a method for generating ex vivo MHCII restricted CD4+ Foxp3+ regulatory T cells having the following phenotype: CD3+ CD4+ Foxp3+.

Abstract: The present invention relates to a method for ex vivo generating and expanding ?? Foxp3+ regulatory T cells, and therapeutic uses thereof. The inventors performed the induction of Foxp3? expression in ex vivo human induced tumor-antigen specific CD4+ TCR?? unrestricted T cells and the induction of autologous CD8-mediated T-cell responses against tumor-antigen specific FOXP3 expressing CD4+ TCR?? unrestricted T cells. The inventors developed a method to ex vivo generated and expanded antigen specific Foxp3 expressing CD3+ TCR?? unrestricted T cells, committed to exclusively exert regulatory activity, whichever culture condition of stimulation is. In particular, the present invention relates to a method for generating ex vivo ?? Foxp3+ regulatory T cells having the following phenotype: CD3+ TCR?? Foxp3+.

Abstract: The invention concerns a pharmaceutical composition comprising, as the active ingredient, human natural antibodies of the IgG isotype, that neutralize the activity of a human cytokine selected from VEGF, IFN?, IL-4, TNF? and TGF?, the said neutralizing antibodies inhibiting at least 50% of the maximum biological activity induced by an amount ranging from 0.006 ng to 0.05 ng of the said cytokine in vitro.

Abstract: A stable immunogenic product for the induction of antibodies against one or more antigenic proteins in a subject, characterized in that it comprises proteinaceous immunogenic heterocomplexes which are formed by associations between (i) antigenic protein molecules and (ii) proteinaceous carrier molecules and in that less than 40% of the antigenic proteins (i) are linked to the proteinaceous carrier molecules (ii) by a covalent bond.

Abstract: The invention concerns vaccines comprising as an active principle an immunogen which is a cytokinetic factor or a cell regulating factor particularly transcriptional or another type of factor with immunosuppressive/apoptotic/angiogenic properties abnormally released in the extracellular (stromal) environment by cancer or stromal cells of malignant tumors, and a pharmaceutically acceptable carrier for inducing a systemic or mucosal immune response with secretory formation of class IgC or IgA neutralizing antibodies directed against the native factor, or which is derived from such a factor and the use of said immunogen to obtain a medicine for use as anticancer drug.

Abstract: The present invention concerns a novel method for preparing a stable immunogenic product comprising antigenic heterocomplexes of TNF? and a carrier protein, the method steps of which are disclosed in the specification.

Abstract: The present invention concerns a novel method for preparing a stable immunogenic product comprising antigenic heterocomplexes of TNF? and a carrier protein, the method steps of which are disclosed in the specification.

Abstract: The invention concerns vaccines comprising as an active principle an immunogen which is a cytokinetic factor or a cell regulating factor particularly transcriptional or another type of factor with immunosuppressive/apoptotic/angiogenic properties abnormally released in the extracellular (stromal) environment by cancer or stromal cells of malignant tumors, and a pharmaceutically acceptable carrier for inducing a systemic or mucosal immune response with secretory formation of class IgC or IgA neutralizing antibodies directed against the native factor, or which is derived from such a factor and the use of said immunogen to obtain a medicine for use as anticancer drug.

Abstract: The invention relates to an immunogenic or vaccine composition inducing an immune response towards the HPV-16 Papillomavirus native E7 protein, without simultaneously inducing an immunosuppression, said composition comprising, as the active ingredient, a non immunosuppressive mutated E7 protein, comprising the amino acid sequence consisting, from the N-terminal end to the C-terminal end, in: i. the 1-19 amino acid sequence of sequence SEQ ID No. 3; ii. an amino acid sequence possessing (a) the substitution of at least one amino acid, compared to the 20-29 corresponding amino acid sequence of sequence SEQ ID No. 3 or (b) the deletion of at least four consecutive amino acids, compared to the 20-29 corresponding amino acid sequence of sequence SEQ ID No. 3; and iii. the 30-98 amino acid sequence of sequence SEQ ID No 3.

Abstract: The invention concerns a pharmaceutical composition comprising, as the active ingredient, human natural antibodies of the IgG isotype, that neutralize the activity of a human cytokine selected from VEGF, IFN?, IL-4, TNF? and TGF?, the said neutralizing antibodies inhibiting at least 50% of the maximum biological activity induced by an amount ranging from 0.006 ng to 0.05 ng of the said cytokine in vitro.

Abstract: The invention relates to an immunogenic or vaccine composition inducing an immune response towards the HPV-16 Papillomavirus native E7 protein, without simultaneously inducing an immunosuppression, said composition comprising, as the active ingredient, a non immunosuppressive mutated E7 protein, comprising the amino acid sequence consisting, from the N-terminal end to the C-terminal end, in: i. the 1-19 amino acid sequence of sequence SEQ ID No. 3; ii. an amino acid sequence possessing (a) the substitution of at least one amino acid, compared to the 20-29 corresponding amino acid sequence of sequence SEQ ID No. 3 or (b) the deletion of at least four consecutive amino acids, compared to the 20-29 corresponding amino acid sequence of sequence SEQ ID No. 3; and iii. the 30-98 amino acid sequence of sequence SEQ ID No.

Abstract: A stable immunogenic product for the induction of antibodies against one or more antigenic proteins in a subject, characterized in that it comprises proteinaceous immunogenic heterocomplexes which are formed by associations between (i) antigenic protein molecules and (ii) proteinaceous carrier molecules and in that less than 40% of the antigenic proteins (i) are linked to the proteinaceous carrier molecules (ii) by a covalent bond.

Abstract: The invention is relative to novel means of systemic or mucosal vaccinial therapy against some cancers, viral infections and allergy which are provided by the invention under the form of a family of composite superimmunogenic compounds for bifunctional vaccinial use able to induce an immune response raised towards two distinct targets, respectively, the causal pathogenic antigenic structure, on the one hand, and locally produced factors responsible for a subsequent immunotoxic or neoangiogenic stroma disorder, on the other hand.

Abstract: The invention concerns vaccines comprising as active principle an immunogen which is a cytokinetic factor or a cell regulating factor particularly transcriptional or another type of factor with immunosuppressive/apoptotic/angiogenic properties abnormally released in the extracellular (stromal) environment by cancer or stromal cells of malignant tumours, and a pharmaceutically acceptable carrier for inducing a systemic or mucosal immune response with secretory formation of class IgC or IgA neutralising antibodies directed against the native factor, or which is derived from such a factor and the use of said immunogen to obtain a medicine for use as anticancer drug.