Medimmune Limited

Amplimmune, Inc.

Johns Hopkins University

Nextcure, Inc.

Washington University

The University of British Columbia

Solomon Langermann

Linda Liu

Shannon Marshall

Sheng Yao

Lieping Chen

Scott J Hultgren

Scott Koenig

Michael Scott Kinch

Peter Kiener

Stephen D Miller

Christine Auguste

Joseph R Podojil

Dallas Benjamin Flies

Jerome Pinkner

John Smit

Nilofer Qureshi

Kelly Carles-Kinch

Frederic G Sauer

Jeanne Burlein

Michael Glen Overstreet

Benjamin Dallas Flies

Andrew Revel

Compositions and methods of use thereof for modulating B7-H4 are provided. For example, immunomodulatory agents are provided that reduce B7-H4 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to increase an immune response in a subject in need thereof. Immunomodulatory agents are also provided that increase B7-H4 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to reduce an immune response in a subject in need thereof.

B7-H4 antibodies and methods of use thereof

Compositions and methods of use thereof for modulating LAIR-1 are provided. For example, immunomodulatory agents are provided that reduce LAIR-1 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to increase an immune response in a subject in need thereof. Exemplary agents include (i) a soluble LAIR-2 polypeptide or fusion protein, (ii) a soluble LAIR-1 polypeptide or fusion protein, (iii) a function blocking anti-LAIR-1 antibody, (iv) an antibody that depletes LAIR-1 positive cells, and (y) combinations thereof. Immunomodulatory agents are also provided that increase LAIR-1 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to reduce an immune response in a subject in need thereof. Exemplary agents include: (i) a function activating anti-LAIR-1 antibody, (ii) a function blocking anti-LAIR-2 antibody, and (iii) a combination thereof.

Compositions and methods for modulating LAIR signal transduction

Siglec-15 binding molecules are provides. The molecules are typically an antibody or antigen binding fragment thereof that immunospecifically binds to Siglec-15. Siglec-15 ligand-binding molecules are also provided. The molecules are typically Siglec-15 polypeptide or fusion protein. Methods of using the molecules to reduce Siglec-15 mediated immunosuppression in a subject in need thereof are also provided.

Antibodies for Siglec-15 and methods of use thereof

The present invention relates to antibodies and their antigen-binding fragments and to other molecules that are capable of immunospecifically binding to the B7-H5 ligand of the B7-H5:CD28H pathway, and to the uses of such molecules in the treatment and diagnosis of autoimmune disease, transplant rejection and other inflammatory diseases.

Anti-B7-H5 antibodies and their uses

Fusion proteins containing B7-H4 polypeptides are disclosed. The B7-H4 fusion proteins can include full-length B7-H4 polypeptides, or can contain a fragment of a full-length B7-H4 polypeptide, including some or all of the extracellular domain of the B7-H4 polypeptide. Methods for using the fusion proteins to downregulate T cell activation and for the treatment of inflammatory and autoimmune diseases and disorders are also disclosed. The B7-H4 fusion proteins are useful for treating inflammation by inhibiting or reducing differentiation, proliferation, activity, and/or cytokine production and/or secretion by ThI, ThI 7, Th22, and/or other cells that secrete, or cause other cells to secrete, inflammatory molecules, including, but not limited to, IL-1&#x3b2;, TNF-&#x3b1;, TGF-beta, IFN-&#x3b3;, IL-17, IL-6, IL-23, IL-22, IL-21, and MMPs; or enhancing IL-IO secretion by Tregs, increasing the differentiation of Tregs, increasing the number of Tregs, or combinations thereof.

B7-H4 fusion proteins and methods of use thereof

Antibodies and humanized variants thereof and their antigen-binding fragments and to other molecules that are capable of immunospecifically binding to the B7-H7 counter-receptor, H7CR, and their uses in enhancing immune responses and the treatment and diagnosis of cancer and other diseases are provided.

Anti-H7CR antibodies

The present invention relates to antibodies (including anti-B7-H4 antibodies) and their antigen-binding fragments and to other molecules (including fusion proteins that bind to the cognate antigen/receptor, etc.) that are capable of immunospecifically binding to B7-H4 and the uses of such molecules in the diagnosis and the treatment of cancer and other diseases. The invention particularly concerns the use of such molecules to retard or prevent tumor growth, inhibit tumor-mediated suppression, eliminate tumors and/or deplete or block the activity of tumor associated macrophages ('TAMs') so as to alter their activity and/or decrease TAM&#x2014;mediated immune suppression.

Anti-B7-H4 antibodies and their uses

Anti-human B7-H4 antibody '6H3', antigen-binding fragments, derivatives, and humanized variants thereof that are capable of immunospecifically binding to B7-H4, and the uses of such molecules in the diagnosis and the treatment of cancer and other diseases are disclosed. In preferred embodiments, the molecules are used to retard or prevent tumor growth, inhibit tumor-mediated suppression, eliminate tumors and/or deplete or block the activity of tumor-associated macrophages ('TAMs') so as to alter their activity and/or decrease TAM-mediated immune suppression.

Anti-human B7-H4 antibodies and their uses

The present invention relates to antibodies and their antigen-binding fragments and to other molecules that are capable of immunospecifically binding to B7-H1 or PD-1. In some embodiments such molecules are additionally capable of modulating the ability of B7-H1 or B7-DC to bind to PD-1 or are capable of affecting the signaling activity of the B7-H1 or PD-1. The invention additionally concerns the uses of such molecules in the diagnosis and treatment of cancer and other diseases.

Antibodies and other molecules that bind B7-H1 and PD-1

Methods for modulating immune responses in a subject are provided. A preferred embodiment provides methods and compositions for reducing or inhibiting transplant rejection in a subject, preferably a human subject. Transplant rejection can be inhibited or reduced in a subject by administering an effective amount of B7-H4 polypeptide, fragments or fusions thereof to inhibit or reduce the biological activity of an immune cell or to reduce the amounts of proinflammatory molecules at a site of transplant. Th1, Th17 and Th22 cells are exemplary T cells that can be targeted for inhibition by B7-H4 polypeptides, fusion proteins or fragments thereof to inhibit or reduce inflammation.

Methods and compositions for the inhibition of transplant rejection

Methods of treating cancer and infectious diseases utilizing a treatment regimen comprising administering a compound that reduces inhibitory signal transduction in T cells, in combination with a potentiating agent, such as cyclophosphamide, to produce potent T cell mediated responses, are described. Compositions comprising the PD-1 antagonists and potentiating agents useful in the methods of the invention are also disclosed.

Compositions of PD-1 antagonists and methods of use

A protein construct comprising a pilus protein portion, preferably a structurally stabilized pilus-protein, and an additional, or effector, portion other than a pilus protein or chaperone and wherein said effector portion serves to stabilize the pilus protein portion and to confer a therapeutic activity, such as vaccine activity or anti-microbial or anticancer activity, on the protein construct is disclosed. Such effector portion commonly comprises a donor strand complementary segment capable of structurally stabilizing a pilus protein subunit and attaching the auxiliary portion to said subunit to form the pilus protein analog of the invention. Methods of using said protein constructs are also disclosed as well as the formation and use of analogs comprising fragments of a pilus protein linked to effector components to produce immunogenic and/or therapeutic activity.

Growing community of inventors

Baltimore, MD, United States of America

Solomon Langermann