Modulation of complement-dependent cytotoxicity through modifications of the C-terminus of antibody heavy chains
View Patent ↗Provided are antibody variants having decreased or increased ability to mediate complement-dependent cytotoxicity (CDC) due to the presence or absence of C-terminal lysines of their heavy chains. Also provided are methods of generating such antibodies, as well as nucleotide constructs and host cells suitable for the production of such antibodies.
1. A method for increasing the ability of a purified IgG antibody which has one C-terminal lysine residue on each heavy chain to mediate complement-dependent cytotoxicity, comprising removing the C-terminal lysine residue from the heavy-chains of the antibody by digestion with a carboxypeptidase, wherein the antibody exhibits increased complement-dependent cytotoxicity compared to the same antibody which was not subjected to digestion with the carboxypeptidase, wherein the carboxypeptidase is carboxypeptidase B or N.
2. The method according to claim 1 , wherein said antibody is of the IgG1 or IgG2 isotype.
3. The method according to claim 2 , wherein said antibody is of the IgG1 isotype.
4. The method according to claim 1 , wherein the antibody is a monospecific antibody.
5. The method according to claim 1 , wherein the antibody is a bispecific antibody.
6. The method according to claim 1 , wherein the antibody is a chimeric, humanized, or human antibody.