NON PEPTIDIC HETEROBIVALENT MOLECULES FOR TREATING INFLAMMATORY DISEASES
The present invention relates to non peptidic, heterobivalent molecules (HBM) that are able to simultaneously bind a surface target protein as well as an endogenous or exogenous human antibody protein and induce immune effector function. More specifically, the present invention relates to agents capable of binding to a chemokine receptor and inducing the depletion of chemokine receptor positive subsets of pathogenic cells in a subject for use in the treatment and/or prevention of cancer, inflammatory, autoimmune and allergic disease.
1 . A method of destroying CCR-positive cells in a human, the method comprising administering to the human a Heterobivalent Molecule (HBM), wherein the HBM comprises a moiety binding to a CCR receptor on the cell and a moiety binding to endogenous or exogenous antibodies.
2 . The method of claim 1 wherein the HBM further comprises a linker.
3 . The method of claim 1 in which the cell destruction is mediated through ADCC, ADCP and/or CDC.
4 . The method of claim 1 in which the CCR-positive cells being destroyed are cancer cells and/or pathogenic immune cells.
5 . The method of claim 1 in which the CCR-positive cells being destroyed are pathogenic immune cells.
6 . The method of claim 4 in which the cancer cells and/or pathogenic immune cells express one or more CCR receptors selected from the group of CCR1, CCR2, CCR3, and CCR5.
7 . The method of claim 6 in which the CCR receptor is CCR1.
8 . The method of claim 6 in which the CCR receptor is CCR2.
9 . The method of claim 6 in which the CCR receptor is CCR3.
10 . The method of claim 6 in which the CCR receptor is CCR5.
11 . The method of claim 1 in which the moiety binding to endogenous or exogenous antibody is selected from the group consisting of DNP, fluorescein, cotinine and biotin.
12 . A method of treating or preventing cancers, inflammatory disease, autoimmune disease, or allergic disease in a human patient comprising administering to the human patient a therapeutically effective amount of a Heterobivalent Molecule (HBM), wherein the HBM comprises a moiety binding to a CCR receptor on a cell and a moiety binding to endogenous or exogenous antibodies.
13 . The method of claim 1 in which the HBM is administered orally.
14 . A pharmaceutical composition comprising a Heterobivalent Molecule (HBM) and one or more pharmaceutically acceptable excipients, carriers, and/or diluents, wherein the HBM comprises a moiety binding to a CCR receptor on a cell and a moiety binding to endogenous or exogenous antibodies.