VEGFR-antibody light chain fusion protein
The present application provides an antibody fusion protein comprising a vascular endothelial growth factor receptor (VEGFR) fused to the C-terminus of the antibody light chain. Also provided are methods of making and using these antibody fusion proteins.
1. An antibody fusion protein comprising 1) an antibody comprising a first light chain and a second light chain, and 2) a first vascular endothelial growth factor receptor (VEGFR) component and a second VEGFR component, wherein the first VEGFR component is fused to the C-terminus of the first light chain, and the second VEGFR component is fused to the C-terminus of the second light chain; wherein the first VEGFR component and the second VEGFR component each comprises the amino acid sequence of SEQ ID NO: 8; and wherein the antibody specifically recognizes an immune checkpoint molecule, a tumor antigen, or an angiogenic factor.
2. The antibody fusion protein of claim 1 , wherein the first VEGFR component and the second VEGFR component are the same.
3. The antibody fusion protein of claim 1 , wherein the first VEGFR component and the second VEGFR component are different.
4. The antibody fusion protein of claim 1 , wherein the first VEGFR component and the C-terminus of the first light chain are connected by a linker, and/or wherein the second VEGFR component and the C-terminus of the second light chain are connected by a linker.
5. The antibody fusion protein of claim 4 , wherein the linker comprises the amino acid sequence of SEQ ID NO: 6 or 7.
6. The antibody fusion protein of claim 1 , wherein the first light chain comprises a first light chain constant domain (CL domain), wherein the second light chain comprises a second CL, wherein the first VEGFR component is fused to the C-terminus of the first CL domain, and wherein the second VEGFR component is fused to the C-terminus of the second CL domain.
7. The antibody fusion protein of claim 1 , wherein the antibody is a full length antibody.
8. The antibody fusion protein of claim 1 , wherein the antibody specifically recognizes an immune checkpoint molecule.
9. The antibody fusion protein of claim 8 , wherein the immune checkpoint molecule is PD-1, PD-L1, or CTLA-4.
10. The antibody fusion protein of claim 8 ,
(i) wherein the immune checkpoint molecule is PD-1, and wherein the antibody comprises: heavy chain-CDR1 (HC-CDR1), HC-CDR2, and HC-CDR3 of a heavy chain comprising the amino acid sequence of SEQ ID NO: 12; and/or light chain-CDR1 (LC-CDR1), LC-CDR2, and LC-CDR3 of a light chain comprising the amino acid sequence of SEQ ID NO: 13;
(ii) wherein the immune checkpoint molecule is PD-1, and wherein the antibody comprises: HC-CDR1, HC-CDR2, and HC-CDR3 of a heavy chain comprising the amino acid sequence of SEQ ID NO: 15; and/or LC-CDR1, LC-CDR2, and LC-CDR3 of a light chain comprising the amino acid sequence of SEQ ID NO: 16;
(iii) wherein the immune checkpoint molecule is PD-L1, and wherein the antibody comprises: HC-CDR1, HC-CDR2, and HC-CDR3 of a heavy chain comprising the amino acid sequence of SEQ ID NO: 18; and/or LC-CDR1, LC-CDR2, and LC-CDR3 of a light chain comprising the amino acid sequence of SEQ ID NO: 19;
(iv) wherein the immune checkpoint molecule is PD-L1, and wherein the antibody comprises: HC-CDR1, HC-CDR2, and HC-CDR3 of a heavy chain comprising the amino acid sequence of SEQ ID NO: 21; and/or LC-CDR1, LC-CDR2, and LC-CDR3 of a light chain comprising the amino acid sequence of SEQ ID NO: 22; or
(v) wherein the immune checkpoint molecule is CTLA-4, and wherein the antibody comprises: HC-CDR1, HC-CDR2, and HC-CDR3 of a heavy chain comprising the amino acid sequence of SEQ ID NO: 9; and/or LC-CDR1, LC-CDR2, and LC-CDR3 of a light chain comprising the amino acid sequence of SEQ ID NO: 10.
11. The antibody fusion protein of claim 1 , wherein the antibody specifically recognizes a tumor antigen.
12. The antibody fusion protein of claim 11 , wherein the tumor antigen is HER2 or EGFR.
13. The antibody fusion protein of claim 11 ,
(i) wherein the tumor antigen is HER2, and wherein the antibody comprises: HC-CDR1, HC-CDR2, and HC-CDR3 of a heavy chain comprising the amino acid sequence of SEQ ID NO: 24; and/or LC-CDR1, LC-CDR2, and LC-CDR3 of a light chain comprising the amino acid sequence of SEQ ID NO: 25; or
(ii) wherein the tumor antigen is EGFR (HER1), and wherein the antibody comprises: HC-CDR1, HC-CDR2, and HC-CDR3 of a heavy chain comprising the amino acid sequence of SEQ ID NO: 29; and/or LC-CDR1, LC-CDR2, and LC-CDR3 of a light chain comprising the amino acid sequence of SEQ ID NO: 30.
14. The antibody fusion protein of claim 1 , wherein the antibody specifically recognizes an angiogenic factor.
15. The antibody fusion protein of claim 14 , wherein the angiogenic factor is Ang2, TNFα, or IL-17A.
16. The antibody fusion protein of claim 14 ,
(i) wherein the angiogenic factor is Angiopoietin-2 (Ang2), and wherein the antibody comprises: HC-CDR1, HC-CDR2, and HC-CDR3 of a heavy chain comprising the amino acid sequence of SEQ ID NO: 35; and/or LC-CDR1, LC-CDR2, and LC-CDR3 of a light chain comprising the amino acid sequence of SEQ ID NO: 36;
(ii) wherein the angiogenic factor is TNFα, and wherein the antibody comprises: HC-CDR1, HC-CDR2, and HC-CDR3 of a heavy chain comprising the amino acid sequence of SEQ ID NO: 32; and/or LC-CDR1, LC-CDR2, and LC-CDR3 of a light chain comprising the amino acid sequence of SEQ ID NO: 33; or
(iii) wherein the angiogenic factor is IL-17A, and wherein the antibody comprises: HC-CDR1, HC-CDR2, and HC-CDR3 of a heavy chain comprising the amino acid sequence of SEQ ID NO: 38; and/or LC-CDR1, LC-CDR2, and LC-CDR3 of a light chain comprising the amino acid sequence of SEQ ID NO: 39.
17. A pharmaceutical composition comprising the antibody fusion protein of claim 1 , and a pharmaceutical acceptable carrier.