Methods for targeted in vitro and in vivo drug delivery to mammalian cells via bacterially derived intact minicells

Abstract

A composition comprising intact minicells that contain a drug molecule is useful for targeted drug delivery. One targeted drug delivery method employs bispecific ligands, comprising a first arm that carries specificity for a bacterially derived minicell surface structure and a second arm that carries specificity for a mammalian cell surface receptor, to target drug-loaded minicells to specific mammalian cells and to cause endocytosis of the minicells by the mammalian cells. Another drug delivery method exploits the natural ability of phagocytic mammalian cells to engulf minicells without the use of bispecific ligands.

1 .- 38 . (canceled) 
     
     
         39 . A method of preventing or treating a disease or condition in a subject using a eubacterial minicell, comprising administering to the subject the eubacterial minicell, wherein the minicell is a fully intact eubacterial minicell derived from a eubacterial parent cell, wherein the minicell comprises a biologically active compound and displays an antibody or antibody derivative, wherein the biologically active compound and antibody or antibody derivative are exogenous to the parent cell and distinct from each other, and wherein the disease or condition is a hyperproliferative disease or disorder. 
     
     
         40 . The method of  claim 39 , wherein said antibody or antibody derivative is an antibody. 
     
     
         41 . The method of  claim 39 , wherein said antibody or antibody derivative is an antibody derivative. 
     
     
         42 . The method of  claim 39 , wherein said antibody or antibody derivative is an antibody derivative directed towards EGFR. 
     
     
         43 . The method of  claim 39 , wherein said antibody or antibody derivative is an antibody derivative directed towards HER-2. 
     
     
         44 . The method of  claim 39 , wherein the biologically active compound is selected from the group consisting of a polypeptide, a small molecule, and a nucleic acid. 
     
     
         45 . The method of  claim 39 , wherein the biologically active compound is a small molecule. 
     
     
         46 . The method of  claim 45 , wherein the small molecule is a drug molecule. 
     
     
         47 . The method of  claim 39 , wherein the biologically active compound is a therapeutic nucleic acid. 
     
     
         48 . The method of  claim 47 , wherein the therapeutic nucleic acid comprises a ribozyme. 
     
     
         49 . The method of  claim 39 , wherein the biologically active compound is a therapeutic polypeptide. 
     
     
         50 . The method of  claim 49 , wherein the therapeutic polypeptide is a protein toxin. 
     
     
         51 . The method of  claim 39 , wherein the disease or condition is a pathogenic disease or a genetic disease. 
     
     
         52 . The method of  claim 39 , wherein the hyperproliferative disease or disorder is cancer. 
     
     
         53 . The method of  claim 52 , wherein the cancer is lung cancer, gastrointestinal cancer, melanoma, breast cancer, glioma, astrocytoma, and mesothelioma. 
     
     
         54 . The method of  claim 39 , wherein the minicell is administered to the subject via oral administration, rectal administration, aerosol, parenteral administration, topical administration, subcutaneous administration, pulmonary administration, nasal administration, buccal administration, ocular administration, dermal administration, vaginal administration, or intramuscular administration.