Ose Immunotherapeutics

Institut National De La Sante Et De La Recherche Medicale

Université De Nantes

Effimune

Assistance Publique-hopitaux De Paris

Etablissement Francais Du Sang

Immutep Parc Club Orsay

Université D'angers

Inserm (institut National De La Sante Et De La Recherche Medicale)

Nantes Université

Immutep

Inserm

Bernard Vanhove

Nicolas Poirier

Caroline Mary

Vanessa Gauttier

Virginie Thepenier

Sabrina Pengam

Jean-Paul Soulillou

Géraldine Teppaz

Flora Coulon

Daniel Olive

Frederic Triebel

Sophie Brouard

Frédéric Triebel

Sebastien Maury

Sylvie Chevalier

Elise Chiffoleau

Geraldine Teppaz

Hugues Gascan

José Cohen

Le Hoa Mai

Thomas Haudebourg

Genevieve Laflamme

Caroline Pilon

Brigitte Birebent

Josy-Anne Froger

Yannick Danger

Geneviève Laflamme

The invention relates to antibodies directed against CD127, the alpha chain of the interleukin 7 (IL-7) receptor IL-7R), and which have antagonist properties for IL-7-IL-7R interaction, may present cytotoxic activity against CD127 positive cells but do not increase the maturation of dendritic cells (DCs) induced by TSLP, a cytokine also using CD127 as part of its receptor. Alternatively, or in addition, these antibodies do not induce the internalization of CD127 and/or inhibit the IL7-induced internalization of CD127. According to another aspect of the invention antibodies are provided which recognize a human CD127 epitope comprising sequences from the 2b site of CD127, in particular the epitope comprising comprises the human CD127 sequences of domain D1 and of the 2b site of CD127, in particular the epitope comprises at least one sequence from D1 comprising SEQ ID No: 115 (in particular comprising SEQ ID No: 110) and/or SEQ ID No: 111 and/or a sequence from the 2b site comprising the sequence of SEQ ID No: 116 and optionally also comprises SEQ ID No: 117 (in particular comprises SEQ ID No: 111). The antibodies of the invention are suitable for use in order to remedy to a condition diagnosed in a human patient which results from pathogenesis related to lymphopoiesis, when IL-7 signalling pathways provide contribution to said pathogenesis, especially when an increase in the maturation, more precisely the upregulation of costimulatory molecules, of dendritic cells is undesirable.

Antibodies directed against CD127

The invention pertains to the field of immunotherapy. The present invention provides new uses of anti-SIRPg antibodies for the treatment and/or the prevention of autoimmune disorders or diseases.

Uses of anti-SIRPg antibodies

The invention relates to methods and preparations for sorting out T effector cells from human leukocytes using anti-CD127 antibodies. Accordingly the invention relates to the use of anti-CD127 antibodies enabling discriminative depletion of subpopulations of Tregulatory cells expressing CD127+ at low levels in a population of human T lymphocytes in order to enable the use of the recovered selected cell preparations comprising essentially Teffector cells as lymphocytes and preferably devoid of Tregulatory cells, for improved efficacy in particular when administered to a patient for therapy.

Method effector cells using anti-CD127 antibodies for applications in cell therapy

The present invention provides new anti-SIRPa antibodies able to specifically antagonize the interaction between SIRPa and CD47, without affecting the interaction between SIRPg and CD47, and their uses.

Anti-SIRPa antibodies and their therapeutic applications

The present invention relates to methods for promoting T cells response. The inventors examined the expression and function of CLEC-1 in human DCs and demonstrated for the first time a cell-surface expression. They investigated its functional role following triggering on orchestration of T-cell responses. The inventors showed in vitro and in vivo with CLEC-1 deficient rats and rat CLEC-1 Fc fusion protein that disruption of CLEC-1 signalling enhances in vitro Th17 activation and in vivo enhances T cell priming and Th17 and Th1 activation. In particular, the present invention relates to CLEC-1 antagonists for promoting T cells response in a subject in need thereof.

Method of promoting a t-cell response or treating cancer by administering an antagonist to human c-type lectin-like receptor-1 (CLEC-1)

The invention is in the field of antibodies useful in therapeutic and diagnostics applications targeting CD127, the alpha chain of the IL7 receptor, and provides in particular humanized monoclonal antibodies against CD127, particularly human CD127, therapeutic uses thereof, and diagnostics applications.

Antibodies and polypeptides directed against CD127

The invention is in the field of immunotherapy. The present invention provides antibodies useful in therapeutic and diagnostic applications targeting human SIRPa, said antibodies enhancing the cross-presentation of antigens to T cells. The invention also provides antibodies against specific isoforms of SIRP a and able to disrupt the interaction between those isoforms of SIRP a and human CD47 for use in treating or preventing a disease, or diagnostic applications, and methods for producing and/or selecting anti-human SIRPa antibodies that bind with different affinities to various isoforms of human SIRP members.

Use of anti-human SIRPa v1 antibodies and method for producing anti-SIRPa v1 antibodies

The present invention provides new modified anti-SIRPa antibodies linked to an immunotherapeutic agent which are bifunctional and able to specifically enhance the immune response and uses thereof.

Modified bifunctional anti-human signal regulatory protein alpha (SIRPa) antibody and method of use thereof for treating cancer

Method for treating a pathological condition involving the activation or proliferation of CD127 positive cells with an anti-CD127 antibody

Methods for promoting t cells response by administering an antagonist of human c-type lectin-like receptor 1 (CLEC-1)

The invention relates to recombinant monovalent antibodies which are heterodimers of a first protein chain comprising the variable domain of the heavy chain of an antibody of interest and the CH2 and CH3 domains of an IgG immunoglobulin and a second protein chain comprising the variable domain of the light chain of said immunoglobulin of interest and the CH2 and CH3 domains of said IgG immunoglobulin. These antibodies can be used in particular as therapeutic agents in all cases where monovalent binding to a ligand such a cellular receptor is required.

Recombinant monovalent antibodies

The invention relates to antibodies directed against CD127, the alpha chain of the interleukin 7 (IL-7) receptor IL-7R), and which have antagonist properties for IL-7-IL-7R interaction, may present cytotoxic activity against CD127 positive cells but do not increase the maturation of dendritic cells (DCs) induced by TSLP, a cytokine also using CD127 as part of its receptor. Alternatively, or in addition, these antibodies do not induce the internalization of CD127 and/or inhibit the IL7-induced internalization of CD127. According to another aspect of the invention antibodies are provided which recognize a human CD127 epitope comprising sequences from the 2b site of CD127, in particular the epitope comprising comprises the human CD127 sequences of domain D1 and of the 2b site of CD127, in particular the epitope comprises at least one sequence from D1 comprising SEQ ID No: 115 (in particular comprising SEQ ID No: 10) and/or SEQ ID No: 111 and/or a sequence from the 2b site comprising the sequence of SEQ ID No: 116 and optionally also comprises SEQ ID No: 117 (in particular comprises SEQ ID No: 111). The antibodies of the invention are suitable for use in order to remedy to a condition diagnosed in a human patient which results from pathogenesis related to lymphopoiesis, when IL-7 signalling pathways provide contribution to said pathogenesis, especially when an increase in the maturation, more precisely the upregulation of costimulatory molecules, of dendritic cells is undesirable.

The invention relates to humanized antibodies directed against the human lymphocyte receptor CD28. When used in a monovalent form these antibodies are antagonists, i.e. capable of blocking of the CD28/B7 interaction, without activating CD28. These antibodies can be used in particular as therapeutic agents for blocking T cell activation through the CD28 receptor.

Anti-CD28 humanized antibodies

Growing community of inventors

Reze, France

Bernard Vanhove