Compositions and methods for the depletion of cd5+ cells

A conjugate represented by the formula Ab-Cy, wherein Ab is an antibody or antigen-binding fragment thereof that binds CD5 and Cy is a cytotoxin, wherein the cytotoxin is an amatoxin (Am) represented by formula (IB)

• wherein R1 is H, OH, ORA, or ORC;
• R2 is H, OH, ORB, or ORC;
• RA and RB, when present, together with the oxygen atoms to which they are bound, combine to form an optionally substituted 5-membered heterocyclolalkyl group;
• R3 is H, RC, or RD;
• R4, R5, R6 and R7, are each independently H, OH, ORC, ORD, RC, or RD;
• R8 is OH, NH2, ORC, ORD, NHRC, or NRCRD;
• R9 is H, OH, ORC, or ORD;
• X is —S—, —S(O)—, or —SO2—;
• RC is -L-Z;
• RD is optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C2-C6 heteroalkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
• L is optionally substituted C1-C6 alkylene, optionally substituted C1-C6 heteroalkylene, optionally substituted C2-C6 alkenylene, optionally substituted C2-C6 heteroalkenylene, optionally substituted C2-C6 alkynylene, optionally substituted C2-C6 heteroalkynylene, optionally substituted cycloalkylene, optionally substituted heterocycloalkylene, optionally substituted arylene, or optionally substituted heteroarylene;
• a dipeptide, —C(═O)—, a peptide. or a combination thereof;
• and
• Z is a chemical moiety formed from a coupling reaction between a reactive substituent present on L and a reactive substituent present within the antibody or antigen-binding fragment thereof,
• wherein Am comprises exactly one RC substituent.