CHEMICAL COMPOUNDS

摘要

Antibody Directed Enzyme Prodrug Therapy (ADEPT) systems for use in cancer based on mutated carboxypeptidase B (CPB) enzymes. Enzyme conjugates for ADEPT are substantially non-immunogenic in humans comprising a targeting moiety (for example an antibody) capable of binding with a tumour associated antigen, the targeting moiety being linked to a mutated form of a CPB enzyme capable of converting a prodrug into an antineoplastic drug wherein the prodrug is not significantly convertible into antineoplastic drug in humans by natural unmutated enzyme. A preferred enzyme mutant is human pancreatic CPB comprising a Lys or Arg residue at position 253. Suitable mustard prodrugs are disclosed in the specification.