USE OF ANTI-CD1 ANTIBODIES FOR THE MODULATION OF IMMUNE RESPONSES
The invention provides methods for the administration of an anti-CD1 antibody for the treatment or prevention of a variety of disorders, such as autoimmune disease, viral infection, bacterial infection, parasitic infection, infection by a eukaryotic pathogen, allergy, asthma, inflammatory condition, graft versus host disease, graft rejection, immunodeficiency disease, spontaneous abortion, pregnancy, and cancer.
1 - 24 . (canceled)
25 . A method of preventing, stabilizing, or treating allergy or asthma in a mammal in need thereof, said method comprising administering to said mammal an anti-CD1 antibody or antibody fragment in an amount sufficient to prevent, stabilize, or treat said allergy or asthma.
26 . The method of claim 25 , wherein said administering is at a dosage level that allows retention of at least 50% of the activity of CD1-reactive T cells in said mammal relative to an untreated mammal.
27 . The method of claim 25 , wherein said administration increases the amount of TGF-β or IL-10 and/or decreases the amount of IL-12, TNF, and/or IFN-γ.
28 . The method of claim 25 , wherein said administering is oral, intramuscular, intravenous, intraarticular, intralesional, subcutaneous, or intraperitoneal.
29 . The method of claim 25 , wherein said antibody or antibody fragment is administered with a pharmaceutically suitable carrier.
30 . The method of claim 25 , wherein said antibody or antibody fragment is an anti-CD1a antibody, an anti-CD1b antibody, an anti-CD1c antibody, or an anti-CD1d antibody, or antibody fragments thereof.
31 . The method of claim 25 , wherein said mammal is a non-rodent mammal.
32 . The method of claim 25 , further comprising administering one or more cytokines to said mammal.
33 . The method of claim 32 , wherein said cytokine is selected from the group consisting of IL-2, IL-4, IL-7, IL-10, IL-12, IL-13, IL-15, IL-18, IFN-α/β, IFN-γ, and GM-CSF.
34 . The method of claim 32 , wherein said cytokine alters the ratio of Th1/Th2/immune deviation response of T cells in said mammal.
35 . A method of preventing, stabilizing, or treating cancer, type I diabetes, or an immunodeficiency disease in a mammal in need thereof, said method comprising administering to said mammal an anti-CD1 antibody or antibody fragment in an amount sufficient to prevent, stabilize, or treat said cancer, type I diabetes, or immunodeficiency disease.
36 . The method of claim 35 , wherein said administering is in an amount sufficient to increase the number or activity of at least one APC.
37 . The method of claim 36 , wherein said administering is in an amount sufficient to increase the production or secretion of a cytokine by said APC or to increase the proliferation of said APC.
38 . The method of claim 37 , wherein the secretion of a cytokine increases by at least 50%.
39 . The method of claim 37 , wherein said cytokine is IL-2, IL-4, IL-7, IL-10, IL-12, IL-13, IL-15, IL-18, IFN-α/β, IFN-γ, or GM-CSF.
40 . A method of preventing, stabilizing, or treating an autoimmune disease other than lupus and type I diabetes, viral infection, bacterial infection other than a listeria infection, parasitic infection, infection by a eukaryotic pathogen, inflammatory condition, graft versus host disease, graft rejection, spontaneous abortion, or pregnancy in a mammal in need thereof, said method comprising administering to said mammal an anti-CD1 antibody or antibody fragment in an amount sufficient to prevent, stabilize, or treat said autoimmune disease other than lupus and type I diabetes, viral infection, bacterial infection other than a listeria infection, parasitic infection, infection by a eukaryotic pathogen, inflammatory condition, graft versus host disease, graft rejection, spontaneous abortion, or pregnancy.
41 . The method of claim 40 , wherein said antibody or antibody fragment is covalently linked to a toxin, radiolabel, or a molecule which targets host defensive or catabolic processes towards an APC.
42 . The method of claim 40 , wherein said viral infection is a Hepatitis, picornavirus, polio, HIV, or coxacchie infection; or wherein said autoimmune disease other than lupus and type I diabetes is rheumatoid arthritis, pemphigus vulgaris, multiple sclerosis, or gravis.
43 . A method of increasing the number or activity of an antigen-present cell (APC) in a mammal, said method comprising
(a) contacting a CD1-expressing APC with an anti-CD1 antibody or antibody fragment; and
(b) administering said contacted APC to said mammal in an amount sufficient to increase the number or activity of said APC in said mammal; or
(c) administering an anti-CD1 antibody or antibody fragment in an amount sufficient to increase the production or secretion of a cytokine by said APC or to increase the proliferation of said APC.
44 . The method of claim 43 , wherein said APC is from said mammal.
45 . The method of claim 43 , wherein said mammal has a cancer, type I diabetes, an immunodeficiency disease, a viral infection, a bacterial infection, or a parasitic infection.
46 . The method of claim 43 , wherein the secretion of a cytokine increases by at least 50%.
47 . The method of claim 43 , wherein said cytokine is IL-2, IL-4, IL-7, IL-10, IL-12, IL-13, IL-15, IL-18, IFN-α/β, IFN-γ, or GM-CSF.
48 . The method of claim 45 , further comprising administering to said mammal an antigen from an infectious agent, a vaccine, or an adjuvant.
49 . The method of claim 48 , wherein said infectious agent is a bacteria, a virus, or a parasite.
50 . The method of claim 48 , wherein said administering of said antigen from an infectious agent, vaccine, or adjuvant enhances the immune response to said viral infection, bacterial infection, or parasitic infection in said mammal.
51 . A pharmaceutical composition comprising an anti-CD1 antibody or antibody fragment and a vaccine, an adjuvant, or an antigen from an infectious agent.