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

A targeted drug delivery method that comprises

• (a) providing a composition comprising (i) at least 107 intact bacterial minicells, wherein said bacterial minicells are derived from Salmonella typhimurium, are approximately 400 nm in diameter, and are loaded with a therapeutically effective amount of a chemotherapeutic drug, and (ii) a bispecific antibody having specificity for a cancer cell surface receptor and specificity for said minicells, wherein said bispecific antibody is attached to said minicells, wherein said composition is free of membrane blebs of 200 nm or less in size, wherein said composition contains fewer than about 1 contaminating parent bacterial cell per 107 minicells;
• and
• (b) contacting said composition with non-phagocytic cancer cells, such that
• (i) said bispecific antibody causes said minicells to bind to said cancer cells,
• (ii) said minicells are engulfed by said cancer cells, and
• (iii) said chemotherapeutic drug is released into the cytoplasm of said cancer cells.