Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

Neovacs

Medecine Et Innovation

Université Paris Diderot-Paris 7

UniversitÉ De Paris

Helene Le Buanec

Daniel Zagury

Armand Bensussan

Bernard Bizzini

Sophie Duchez

Valerie Schiavon

Jean Francois Zagury

The present invention relates to a method for ex vivo generating and expanding MHCII restricted CD4Foxp3regulatory T cells, and therapeutic uses thereof. The inventors here demonstrated the optimal conditions for inducing Foxp3 expression in naive CD3+ CD4+ TCR&#x3b1;&#x3b2;+ 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&#x3b1;&#x3b2;+ 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+.

Ex vivo generation of MHCII restricted CD4FOXP3regulatory T cells and therapeutic uses thereof

The present invention relates to a method for ex vivo generating and expanding &#x3b3;&#x3b4; Foxp3regulatory T cells, and therapeutic uses thereof. The inventors performed the induction of Foxp3+ expression in ex vivo human induced tumor-antigen specific CD4+ TCR&#x3b3;&#x3b4; unrestricted T cells and the induction of autologous CD8-mediated T-cell responses against tumor-antigen specific FOXP3 expressing CD4+ TCR&#x3b3;&#x3b4; unrestricted T cells. The inventors developed a method to ex vivo generated and expanded antigen specific Foxp3 expressing CD3+ TCR&#x3b3;&#x3b4;+ 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 &#x3b3;&#x3b4; Foxp3+ regulatory T cells having the following phenotype: CD3+ TCR&#x3b3;&#x3b4;+ Foxp3+.

Ex vivo generation of &#x3b3;&#x3b4; Foxp3regulatory T cells and therapeutic uses thereof

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&#x3b1;, IL-4, TNF&#x3b1; and TGF&#x3b2;, 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.

High-yield method for the production of human antibodies blocking the biological activity of a human cytokine

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.

Use of immunogens to treat or prevent, in malignant tumors, the immune or vascular disorders induced by extracellular factors

Growing community of inventors

Paris, France

Helene Le Buanec