Treatment of CD30-positive diseases, such as Hodgkin's lymphoma, by administration of a combination of sheddase inhibitor and anti-CD30 immunotherapeutic agents

Abstract

CD30 is a transmembrane receptor, selectively expressed on tumor cells of certain lymphatic malignancies, such as Hodgkin's lymphoma, and therefore a privileged target for anti-CD30 antibody-based immunotherapy. However, CD30 is cleaved at the cell surface. Thus, the entire ectodomain (sCD30) is released and competes with targeting of tumor-cell-anchored CD30. Cleavage is catalyzed by the metalloproteases ADAM10 and ADAM17, which are therefore also referred to as sheddases. This patent describes a method of treating patients with diseases characterized by expression of CD30 using an anti-CD30 antibody or conjugate and a sheddase inhibitor. It is expected that blocking of the sCD30 release improves tumor cell targeting. Unfortunately, in previous clinical studies, metalloprotease inhibitors caused severe side effects, predominantly due to their lack of selectivity. The application of an inhibitor with improved sheddase selectivity represents a promising approach to ameliorate anti-CD30 immunotherapy.

Keywords::

• CD30
• Hodgkin's lymphoma
• immunotherapy
• sheddase inhibition