CROSS-SPECIES-SPECIFIC PSMAxCD3 BISPECIFIC SINGLE CHAIN ANTIBODY
The present invention relates to a bispecific single chain antibody molecule comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 epsilon chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain capable of binding to prostate-specific membrane antigen (PSMA). The invention also provides nucleic acids encoding said bispecific single chain antibody molecule as well as vectors and host cells and a process for its production. The invention further relates to pharmaceutical compositions comprising said bispecific single chain antibody molecule and medical uses of said bispecific single chain antibody molecule.
1 . A method for treating prostate cancer in a subject having prostate cancer expressing prostate-specific membrane antigen (PSMA) comprising administering to the subject an effective amount of a bispecific single chain antibody molecule, wherein the bispecific single chain antibody molecule comprises a first binding domain that specifically binds to human CD3 epsilon chain and a second binding domain that specifically binds to human PSMA.
2 . The method of claim 1 , wherein at least one of the first binding domain or the second binding domain is a humanized binding domain.
3 . The method of claim 1 , wherein both the first binding domain and the second binding domain are humanized binding domains.
4 . The method of claim 1 , wherein the first binding domain is a single chain variable fragment (scFv) comprising a VH region and a VL region.
5 . The method of claim 4 , wherein the VH and VL regions are arranged in an amino to carboxyl terminal order of VH-VL.
6 . The method of claim 4 , wherein the first binding domain is positioned toward the carboxyl terminus of the molecule relative to the second binding domain.
7 . The method of claim 1 , wherein the second binding domain is a single chain variable fragment (scFv) comprising a VH region and a VL region.
8 . The method of claim 1 , wherein the first binding domain comprises a VH region (VH CD3) and VL region (VL CD3) and the second binding domain comprises a VH region (VH PSMA) and VL region (VL PSMA), wherein the variable regions are arranged in an amino to carboxyl terminal order of VH PSMA-VL PSMA-VH CD3-VL CD3 or VL PSMA-VH PSMA-VH CD3-VL CD3.
9 . The method of claim 1 , wherein the risk of CNS adverse events associated with T cell redistribution is reduced in the subject as compared to the risk of CNS adverse events resulting from administration of a multimeric CD3 binding molecule.
10 . The method of claim 1 , wherein the bispecific single chain antibody molecule is administered in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
11 . The method of claim 1 , wherein the bispecific single chain antibody molecule is administered intravenously.
12 . The method of claim 11 , wherein the bispecific single chain antibody molecule is administered by intravenous infusion.