Dana-Farber-Cancer Institute Inc.

Duke University

Institut National De La Sante Et De La Recherche Medicale

Assistance Publique - Hopitaux De Paris (Aphp)

University of California

Inserm

Thomas F. Tedder

Olivier G. Spertini

Thomas F Tedder

Liang-Ji Zhou

Boris Schleiffenbaum

Olivier Spertini

Koichi Yanaba

Jean-David Bouaziz

Olivier G Spertini

Jonathan C Poe

Yasuhito Hamaguchi

Hanne Gron

Ayumi Yoshizaki

Norihito Yazawa

Tomomitsu Miyagaki

Geoffrey S Kansas

Evgueni Kountikov

Stuart F Schlossman

Alain Tedgui

Hafid Ait-Oufella

Haruo Saito

Takashi Matsushita

Jacquelyn Lykken

Yohei Iwata

Pablo Engel

Mayuka Horikawa

Ziad Mallat

Yasuhiro Fujisawa

Junji Uchida

Joseph Tuscano

Kathleen M Candando

Hiraku Suga

Masahiro Kamata

Hafid Ait-oufella

The present invention relates to the prevention or treatment of atherosclerosis, in particular to a B cell depleting agent for the prevention or treatment of atherosclerosis.

B cell depleting agent for the treatment of atherosclerosis

Provided are methods involving combination therapy comprising administering to an individual in need thereof an antibody that preferentially depletes human B10 cells and an immune checkpoint inhibitor. Antibodies for use in the methods are also provided.

Antibodies and methods for depleting regulatory bio cells and use in combination with immune checkpoint inhibitors

Provided herein are methods of expanding B cells, and in particularly B10 cells capable of producing IL-10, ex vivo. The methods include incubation of harvested B cells in the presence of IL-21. Compositions comprising the ex vivo expanded B cells and methods of using the expanded B cell-containing compositions to treat diseases or conditions are also provided. Methods of assessing B10 cell function in a subject are also provided.

Methods of expanding and assessing B cells and using expanded B cells to treat disease

The present invention relates to a distinct B cell subset, B10 cells, that regulate T cell mediated inflammatory responses through the secretion of interleukin-10 (IL-10). The invention also relates to the use of B10 cells in the manipulation of immune and inflammatory responses, and in the treatment of disease. Therapeutic approaches involving adoptive transfer of B10 cells, or expansion of their endogenous levels for controlling autoimmune or inflammatory diseases and conditions are described. Ablation of B10 cells, or inhibition of their IL-10 production can be used to upregulate immunodeficient conditions, ameliorate infectious diseases and/or to treat tumors/cancer. Diagnostic applications are also encompassed.

Regulatory B cells and their uses

The present invention relates to a phenotypically distinct CD1dCD5B cell subset that regulates T cell mediated inflammatory responses through the secretion of interleukin-10 (IL-10). The invention also relates to the use of these IL-10 producing regulatory B cells in the manipulation of immune and inflammatory responses, and in the treatment of disease. Therapeutic approaches involving adoptive transfer of these regulatory B cells, or expansion of their endogenous levels for controlling autoimmune or inflammatory diseases and conditions are described. Ablation of this subset of regulatory B cells, or inhibition of their IL-10 production can be used to upregulate immunodeficient conditions, and/or to treat tumors/cancer. Diagnostic applications also are encompassed.

Methods of enhancing the effectiveness of an antibody-based therapeutic agent are provided herein. The methods include administering an antibody-based therapeutic and a composition capable of preferentially activating monocytes or macrophages or preferentially depleting B10 cells to a subject in need of such treatment. The subject may have cancer, an autoimmune disease, an infectious disease or an immunodeficiency. The composition capable of preferentially activating monocytes or macrophages may be a TLR3 agonist. The composition capable of preferentially depleting B10 cells may be a CD19 antibody. Pharmaceutical compositions comprising an antibody-based therapeutic agent and a composition capable of preferentially activating monocytes or macrophages or preferentially depleting B10 cells are also provided.

Methods and compositions combining immunotherapy with monocyte activation

The present invention relates to a phenotypically distinct CD1dCD5B cell subset that regulates T cell mediated inflammatory responses through the secretion of interleukin-10 (IL-IO). The invention also relates to the use of these IL-IO producing regulatory B cells in the manipulation of immune and inflammatory responses, and in the treatment of disease. Therapeutic approaches involving adoptive transfer of these regulatory B cells, or expansion of their endogenous levels for controlling autoimmune or inflammatory diseases and conditions are described. Ablation of this subset of regulatory B cells, or inhibition of their IL-IO production can be used to upregulate immunodeficient conditions, and/or to treat tumors/cancer. Diagnostic applications also are encompassed.

The present invention provides monoclonal antibodies and antigen-binding fragments thereof that specifically bind to CD20, as well as pharmaceutical compositions comprising the same. The invention further provides methods of using the monoclonal antibodies, antigen-binding fragments, and pharmaceutical compositions, for example, in methods of depleting B cells or in treating B cell disorders. Also provided are cells, nucleic acids and methods for producing the monoclonal antibodies.

CD-20 specific antibodies and methods of employing same

The invention relates to immunotherapeutic compositions and methods for the treatment of B cell diseases and disorders in human subjects, such as, but not limited to, B cell malignancies and autoimmune diseases and disorders, using therapeutic antibodies that bind to the human CD19 antigen and that preferably mediate human ADCC. The present invention relates to pharmaceutical compositions comprising human or humanized anti-CD19 antibodies of the IgG1 or IgG3 human isotype. The present invention relates to pharmaceutical compositions comprising human or humanized anti-CD19 antibodies of the IgG2 or IgG4 human isotype that preferably mediate human ADCC. The present invention also relates to pharmaceutical compositions comprising chimerized anti-CD19 antibodies of the IgG1, IgG2, IgG3, or IgG4 isotype that mediate human ADCC. In preferred embodiments, the present invention relates to pharmaceutical compositions comprising monoclonal human, humanized, or chimeric anti-CD19 antibodies.

Anti-CD19 antibodies and uses in B cell disorders

The invention concerns treatment methods using anti-CD22 monoclonal antibodies with unique physiologic properties. In particular, the invention concerns methods for the treatment of B-cell malignancies and autoimmune diseases by administering an effective amount of a blocking anti-CD22 monoclonal antibody specifically binding to the first two Ig-like domains, or to an epitope within the first two Ig-like domains of native human CD22 (hCD22).

Reagents and treatment methods for autoimmune diseases

The subject invention relates a method for the production of monoclonal antibodies. The method utilizes an immunized animal having antibody-producing cells with disrupted peripheral tolerance. The invention also provides a method for the use of such monoclonal antibodies, and polyclonal antibodies derived from an immunized animal having antibody-producing cells with disrupted peripheral tolerance, for in vitro and in vivo clinical diagnostics and therapeutics.

Antibody production methods relating to disruption of peripheral tolerance in B lympho-cytes

Human lymphocyte-associated cell surface protein LAM-1, which includes domains homologous with binding domains of animal lectins, growth factors, and C3/C4 binding proteins, and the cDNA encoding LAM-1, are described. Antagonists to LAM-1 are used in a method of treating a human patient suffering from a lymphocyte-mobilizing condition which involves administering a therapeutic amount of the antagonist in a non-toxic pharmaceutical carrier substance. Additionally, antibodies that bind human LAM-1 and inhibit cellular adhesion, migration or infiltration into tissues are described.

Antibodies against lymphocyte-associated cell surface protein LAM-1

A shed form of leukocyte adhesion molecule-1 (LAM-1, L-selectin) is present in high levels in human plasma. Quantitative methods of detecting shed LAM-1 (sLAM-1) by Western blot and ELISA analysis are disclosed. Also disclosed are methods for the specific detection of cell-surface bound LAM-1 in the presence of shed LAM-1 and for immunotherapy using monoclonal antibodies reactive with cell-surface bound LAM-1 but not reactive with shed LAM-1. In addition a method of producing an antibody that is reactive with cell-surface bound LAM-1 but not reactive with shed LAM-1 is disclosed.

Growing community of inventors

Durham, NC, United States of America

Thomas F Tedder