Disclosed are agents inhibiting the interaction between CFH and CD11b/18, as well as the use of such agents, in particular for treating inflammatory disorders, such as age-related macular degeneration.

This disclosure provides for chimeric receptor polypeptides where upon binding of a first antigen to the antigen binding domain triggers a proteolytic cleavage and upregulation of a chimeric antigen receptor, wherein the chimeric antigen receptor binds to a second antigen. The first and second antigens are present on a population of B cells known as Autoimmune- or Age-related B cells or CD11c+T-bet+ B cells. The present disclosure includes methods and compositions for reducing or eliminating ABCs through the binding of the chimeric antigen receptor, and thus controlling or eliminating autoimmune disease.

The present invention provides an isolated monoclonal antibody or an antigen-binding portion thereof which a) binds to Mac-1, b) specifically inhibits the interaction of CD40L with activated Mac-1 and c) does not induce integrin outside-in signaling.

The invention provides compositions and methods for reducing symptoms of inflammation by administering therapeutically effective amounts of (a) (1) enterotoxic E. coli heat labile detoxified toxin A subunit that interferes with the function of ADP-ribosylation factor and inhibits ADP-ribosylation, or (2) A1 subunit that interferes with the function of ADP-ribosylation factor and inhibits ADP-ribosylation, or both (1) and (2), and (b) a carrier that causes internalization of the A subunit or A1 subunit, or both, into cells.

The CD40L/Mac-1 interaction is selectively targeted by small peptide inhibitors and/or antibodies and such peptides are used for the specific treatment of inflammation and atherogenesis. In particular, pharmaceutical compositions comprising a polypeptide having the amino acid sequence EQLKKSKTL and antibodies specifically binding to an epitope are disclosed.

The present invention concerns methods of diagnosing and treating a malignant neoplasm of the CNS by detecting mammalian tissue expressing integrin alpha 10 subunit or a fragment or variant thereof, and administering a drug specific for integrin alpha 10 subunit.

The present invention provides an isolated monoclonal antibody or an antigen-binding portion thereof which a) binds to Mac-1, b) specifically inhibits the interaction of CD40L with activated Mac-1 and c) does not induce integrin outside-in signaling.

The present invention, in some aspects, provides methods, reagents, compositions, and kits for the radiolabeling of proteins, for example, of proteins useful for positron emission tomography (PET) or single-photon emission computed tomography (SPECT) (e.g., for diagnostic and therapeutic applications), using sortase-mediated transpeptidation reactions. Some aspects of this invention provide methods for the conjugation of an agent, for example, a radioactive agent or molecule to diagnostic or therapeutic peptides or proteins. Compositions comprising sortagged, radiolabeled proteins as well as reagents for generating radiolabeled proteins are also provided. Kits comprising reagents useful for the generation of radiolabeled proteins are provided, as are precursor proteins that comprise a sortase recognition motif.

The present invention is based on the finding that CD11b signaling inhibits immune suppression, modulates neovascularization and promotes anti-tumor immune responses in models of murine and human cancer. As such, provided herein are methods of treating cancer using an antibody, protein or small molecule that modulates CD11b activity or expression. Also provided are methods of identifying cancer that is amenable to such treatment and/or increasing susceptibility of cancer cells to treatment with a chemotherapeutic agent.

Compositions and methods for treating sexual dysfunction using i integrin antagonists, intracellular adhesion molecule antagonists, or leukocyte antagonists are described herein.