Heterodimeric antibodies that bind prostate specific membrane antigen (PSMA) and CD3
Provided herein are novel antigen binding domains and antibodies (e.g., heterodimeric antibodies) that bind Prostate Specific Membrane Antigen (PSMA). In exemplary embodiments, the anti-PSMA antibodies also bind CD3. Such antibodies that bind PSMA and CD3 are useful, for example in the treatment of PSMA-related cancer.
1. A heterodimeric antibody comprising:
a) a first monomer comprising, from N-terminus to C-terminus, a VH1-CH1-linker 1-scFv-linker 2-CH2-CH3,
wherein VH1 is a first variable heavy domain, scFv is an anti-CD3 scFV, linker 1 and linker 2 are a first domain linker and second domain linker, respectively, and CH2-CH3 is a first Fc domain;
b) a second monomer comprising, from N-terminus to C-terminus, a VH2-CH1-hinge-CH2-CH3, wherein VH2 is a second variable heavy domain and CH2-CH3 is a second Fc domain; and
c) a first common light chain comprising a first variable light domain (VL1) and a light chain constant domain; and
d) a second common light chain comprising a second variable light domain (VL2) and a light chain constant domain,
wherein the first variable heavy domain and the first variable light domain form a first PSMA binding domain, and the second variable heavy domain and the second variable light domain form a second PSMA binding domain,
wherein the VH1 and VH2 each comprise the vhCDR1, vhCDR2 and vhCDR3 of a variable heavy domain having an amino acid sequence of SEQ ID NO: 217; and the VL1 and VL2 each comprise the vlCDR1, vlCDR2 and vlCDR3 of a variable light domain having an amino acid sequences of one of the following: SEQ ID NO: 252, SEQ ID NO: 257, and SEQ ID NO: 286.
2. A heterodimeric antibody according to claim 1 , wherein the first and second variable heavy domain each have an amino acid sequence of SEQ ID NO: 217, and the first and second variable light domain is each have an amino sequence of one of the following: SEQ ID NO: 252, SEQ ID NO: 257, and SEQ ID NO: 286.
3. A heterodimeric antibody according to claim 1 , wherein the scFv comprises a vhCDR1 having an amino acid sequence of SEQ ID NO: 167, a vhCDR2 having an amino acid sequence of SEQ ID NO: 168, a vhCDR3 having an amino acid sequence of SEQ ID NO: 169, a vlCDR1 having an amino acid sequence of SEQ ID NO: 163, a vlCDR2 having an amino acid sequence of SEQ ID NO: 164, and a vlCDR3 having an amino acid sequence of SEQ ID NO: 165.
4. A heterodimeric antibody according to claim 1 , wherein the scFv comprises a variable heavy domain having an amino acid sequence of SEQ ID NO: 166, and a variable light domain having an amino acid sequence of SEQ ID NO: 162.
5. A heterodimeric antibody according to claim 1 , wherein the first monomer, second monomer, first common light chain, and second common light chain are selected from the group consisting of:
a) a first monomer having an amino acid sequence of SEQ ID NO: 557, a second monomer having an amino acid sequence of SEQ ID NO: 556, a first common light chain having an amino acid sequence of SEQ ID NO: 558, and a second common light chain having an amino acid sequence of SEQ ID NO: 558;
b) a first monomer having an amino acid sequence of SEQ ID NO: 560, a second monomer having an amino acid sequence of SEQ ID NO:559, a first common light chain having an amino acid sequence of SEQ ID NO: 561, and a second common light chain having an amino acid sequence of SEQ ID NO: 561; and
c) a first monomer having an amino acid sequence of SEQ ID NO: 563, a second monomer having an amino acid sequence of SEQ ID NO: 562, a first common light chain having an amino acid sequence of SEQ ID NO: 564, and a second common light chain having an amino acid sequence of SEQ ID NO: 564.
6. A nucleic acid composition comprising:
a) a first nucleic acid encoding the first monomer according to claim 1 ;
b) a second nucleic acid encoding the second monomer according to claim 1 ; and
c) a third nucleic acid encoding the first common light chain, and second common light chain according to claim 1 .
7. An expression vector composition comprising:
a) a first expression vector comprising the first nucleic acid according to claim 6 ;
b) a second expression vector comprising the second nucleic acid according to claim 6 ; and
c) a third expression vector comprising the third nucleic acid according to claim 6 .
8. A host cell transformed with the expression vector composition according to claim 7 .