Method of decreasing cytotoxic side-effects and improving efficacy of immunoconjugates

摘要

Disclosed are methods, compositions and kits for improving targeting, in particular tumor targeting, of immunoconjugates. The method and composition relies on the sequestration of non-target cells that also express the antigen the immunoconjugate targets. Sequestration of those non-target cells in a variety of ways is disclosed. The methods, compositions and kits allow appropriate sequestration of non-target cells while maintaining a high degree of effectiveness of the immunoconjugates against target cells.

主权项

1. A method for improving tumor targeting, of immunoconjugates targeting cell bound CD138 antigen expressed on target cells comprising:
(a) administering to a patient in need thereof an unconjugated antibody, wherein said unconjugated antibody binds to a linear epitope between residues 90-95 of the core protein on human CD138 wherein CD138 is, in the blood of said patient, cell bound on target cells and non-target cells and is also present in soluble form (soluble antigen) and wherein said target cells are cancer cells and; (b) sequestering in said patient cell bound CD138 antigen on target and non-target cell, optionally soluble antigen, and optionally CD138 antigen expressing cells, wherein the cell bound CD138 antigen and soluble CD138 antigen are different configurations of the same CD138 antigen, (c) administering an immunoconjugate targeting said cell bound CD138 antigen expressed on target cells comprising a targeting antibody for said cell bound CD138 antigen that is functionally attached to an effector molecule, wherein said sequestering in (b) improves tumor targeting of said immunoconjugate.