Multivalent antibody complexes targeting IGF-1R show potent toxicity against solid tumors

摘要

The present invention concerns methods and compositions comprising an anti-IGF-1R antibody or fragment thereof for treatment of cancer or autoimmune disease. Preferably, the cancer is renal cell carcinoma, breast cancer or pancreatic cancer. The anti-IGF-1R antibody or fragment may be part of a complex, such as a DOCK-AND-LOCK™ (DNL™) complex. Preferably, the DNL™ complex also comprises a second antibody, a second antibody fragment, an affibody or a cytokine. More preferably, the cytokine is interferon-α2b. Most preferably, the second antibody, second fragment or affibody binds to IGF-1R, TROP2 or CEACAM6. The anti-IGF-1R antibody or complex may be administered alone or in combination with a therapeutic agent, such as an mTOR inhibitor.

主权项

1. A method of treating a cancer that expresses IGF-1R comprising:
a) administering a complex to an individual with the cancer, wherein the complex comprises:
(i) an anti-IGF-1R IgG antibody or antigen-binding fragment thereof attached to one or more anchor domain (AD) moieties from an AKAP protein; and(ii) two or more copies of an effector attached to a dimerization and docking domain (DDD) moiety from a human protein kinase A (PKA) regulatory subunit RIα, RIβ, RIIα or RIIβ, wherein the effector is a second antigen-binding antibody fragment or a cytokine; and b) administering a therapeutic agent to the individual;wherein two copies of the DDD moiety form a dimer that binds to the AD moiety to form the complex.