摘要:
Compositions and methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40-expressing cells, such as B cells.
摘要:
Compositions and methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40-expressing cells, such as B cells.
摘要:
Compositions and methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40-expressing cells, such as B cells.
摘要:
Methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40 expressing cells, such as B cells.
摘要:
Compositions and methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40-expressing cells, such as B cells.
摘要:
Methods of therapy for treating a subject for multiple myeloma are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40 expressing multiple myeloma cells.
摘要:
Methods of treating a human subject for a cancer characterized by neoplastic B cell growth are provided. The methods comprise administering combination antibody therapy to the subject, where an effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof in combination with an anti-CD20 antibody or antigenbinding fragment thereof is administered to the subject. The invention further comprises pharmaceutical compositions with combinations of these antibodies in a pharmaceutically acceptable carrier.
摘要:
Methods of therapy for treating a subject for chronic lymphocytic leukemia are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CN40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40-expressing chronic lymphocytic leukemia cells.
摘要:
Methods for treating a human patient for an inflammatory or autoimmune disease that is associated with CD40-expressing cells are provided, where the human patient is heterozygous or homozygous for FcγRIIIa-158F (genotype V/F or F/F). Also provided are methods of inhibiting antibody production by B cells in a human patient who is heterozygous or homozygous for FcγRIIIa-158F (genotype V/F or F/F). The methods comprise administering to the human patient a therapeutically or prophylactically effective amount of an anti-CD40 antibody. Methods and kits for identifying a human patient with an inflammatory or autoimmune disease that is treatable with an anti-CD40 antibody and which is non-responsive or refractory to treatment with rituximab (Rituxan®), as well as methods and kits for selecting an antibody therapy for treatment of a human patient having an inflammatory or autoimmune disease that is non-responsive or refractory to treatment with rituximab (Rituxan®), are also provided. The methods of the present invention find use in treatment of inflammatory diseases and autoimmune diseases that are associated with CD40-expressing cells. These methods are particularly advantageous with respect to inflammatory diseases and autoimmune diseases that are associated with cells expressing both CD40 and CD20, as the methods enable the treatment of patients having an inflammatory or autoimmune disease that is non-responsive or refractory to therapy with other therapeutic agents such as anti-CD20 antibodies.
摘要:
Methods for identifying subjects having an inflammatory disease and/or autoimmune disease that will benefit from anti-CD40 therapeutic agents that modulate CD40L-mediated CD40 signaling are provided. The methods comprise the use of biomarkers of cellular apoptosis, cell proliferation and survival, and CD40 signaling pathways to monitor ex vivo response to one or more anti-CD40 therapeutic agents of interest that modulate CD40 signaling on CD40-expressing cells. The ex vivo prognostic assays can be used alone or in conjunction with other prognostic assays to identify candidate subjects who will benefit from treatment with anti-CD40 therapeutic agents. Methods of the invention also comprise the use of these biomarkers to monitor in vivo efficacy of treatment with an anti-CD40 therapeutic agent.