Agents targeting CD138 and uses thereof

摘要

Disclosed is a human murine chimeric antibody targeting CD138 which substantially retains the antigen binding region of its murine counterpart. The engineered antibody displays improved binding affinities to the antigen and/or more homogenous binding to target cells relative to its murine counterpart. A constant region of the immunoglobulin heavy chain is preferably an IgG4 isotype constant region.

主权项

1. An engineered targeting antibody which recognizes CD138 comprising
an antigen binding region (ABR) against CD138, wherein said antigen binding region is of a non-human antibody, and a further antibody region, wherein at least part of said further antibody region is of a human antibody, wherein the engineered targeting antibody is of an IgG4 isotype causing the engineered targeting antibody to bind CD138 with a binding affinity that exceeds the binding affinity of said non-human antibody as a result of the IgG4 isotype, wherein the antigen binding region comprises a heavy chain variable region (VH) comprising amino acids 1-122 of SEQ ID NO: 1 or a sequence having at least 95% sequence identity therewith, wherein said VH comprises amino acids 31-35 of SEQ ID NO: 1 (CDR1), amino acids 51-68 of SEQ ID NO: 1 (CDR2) and amino acids 99-111 of SEQ ID NO: 1 (CDR3), and a light chain variable region (VL) comprising amino acids 1-107 of SEQ ID NO: 2 or a sequence having at least 95% sequence identity therewith, wherein said VL comprises amino acids 24-34 of SEQ ID NO: 2 (CDR1), amino acids 50-56 of SEQ ID NO: 2 (CDR2) and amino acids 89-97 of SEQ ID NO. 2 (CDR3).