Recombinant protein targeting PD-L1 and VEGF
View Patent ↗Disclosed is a recombinant protein containing 1) an anti-PD-L1 antibody heavy chain and an anti-PD-L1 antibody light chain, which two are linked by a disulfide bond to bind PD-L1, and 2) an extracellular Ig-like domain of a vascular epithelial growth factor receptor (VEGFR), linked via a linker to the N-terminus or C-terminus of the heavy chain or the light chain, wherein the recombinant protein is capable of binding PD-L1, VEGF and Fc receptor simultaneously. Also disclosed are a recombinant antibody containing two recombinant proteins of the disclosure, a polynucleotide encoding the recombinant protein, an expression vector containing the polynucleotide, a method for producing the recombinant protein and a method for treating a disease caused by over expression of VEGF and/or PD-L1 using the recombinant protein.
1. A recombinant protein, comprising
an anti-PD-L1 antibody comprising a heavy chain and a light chain, and
an extracellular Ig-like domain of a vascular epithelial growth factor receptor (VEGFR), linked via a linker to N-terminus of the heavy chain,
wherein the heavy chain comprises SEQ ID NO: 2, and the light chain SEQ ID NO: 6,
wherein the extracellular Ig-like domain of VEGFR is a second extracellular Ig-like domain of VEGFR1 and comprises SEQ ID NO: 8,
wherein the linker comprises SEQ ID NO: 12, and
wherein the recombinant protein is capable of binding PD-L1, VEGF and Fc receptor simultaneously.
2. The recombinant protein according to claim 1 , wherein the anti-PD-L1 antibody is Atezolizumab.
3. The recombinant protein according to claim 1 , wherein the heavy chain with the extracellular Ig-like domain of VEGFR comprises SEQ ID NO.:14.
4. A polynucleotide encoding the recombinant protein according to claim 1 .
5. A vector containing the polynucleotide according to claim 4 .
6. A host cell containing the vector according to claim 5 .
7. A pharmaceutical composition, comprising the recombinant protein according to claim 1 , and a pharmaceutically acceptable carrier.
8. A method for treating a disease caused by over-expression of VEGF or PD-L1, or both, selected from group consisting of breast cancer, lung cancer and colon cancer, comprising administering to a patient or a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 7 .