Recombinant bifunctional protein targeting CD47 and HER2
View Patent ↗The present disclosure provides a recombinant fusion protein containing an extracellular Ig-like domain of a signal-regulator protein (SIRP), linked via a linker, to a paratope of an Ig-like anti-HER2 antibody at the N-terminus of a heavy chain or a light chain constituting the paratope. The present disclosure also provides a polynucleotide encoding the recombinant fusion 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 CD47 and/or HER2.
1. A recombinant fusion protein, comprising SEQ ID NO: 2, a linker comprising a peptide of 10 to 30 amino acid residues, and an anti-HER2 antibody, wherein every paratope of the anti-HER2 antibody is linked to SEQ ID NO: 2 at the N-terminus of the light chain constituting the paratope, and wherein the anti-HER2 antibody heavy chains comprise SEQ ID NO:6 and the anti-HER2 antibody light chains comprise SEQ ID NO:8, and the recombinant fusion protein is capable of blocking binding of CD47s on cancer cells to signal-regulatory proteins (SIRPs) on surfaces of macrophages, binding to HER2s on cancer cells to inhibit uncontrolled cancer cell growth, and binding to FcRs on NK cells or macrophages.
2. The recombinant fusion protein of claim 1 , wherein the linker is -(Gly-Gly-Gly-Gly-Ser) 3 - (SEQ ID NO: 4).
3. A polynucleotide encoding the recombinant fusion protein of claim 1 .
4. An expression vector comprising the polynucleotide of claim 3 .
5. A host cell comprising the expression vector of claim 4 .
6. A pharmaceutical composition, comprising the recombinant fusion protein of claim 1 , and at least one pharmaceutical carrier.
7. The recombinant fusion protein of claim 1 , the anti-HER2 antibody is a monoclonal antibody.
8. The recombinant fusion protein of claim 7 , wherein the anti-HER2 antibody is Trastuzumab.
9. A method for treating a cancer, wherein cells of the cancer over-express CD47 and/or HER2, comprising administering to a patient or a subject a therapeutically effective amount of the pharmaceutical composition of claim 6 .
10. The method of claim 9 , wherein the cancer is selected from the group consisting of acute myelocytic leukemia (AML), chronic myelocytic leukemia (CIVIL), acute lymphoblastic leukemia (ALL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), bladder cancer, ovarian cancer, prostate cancer, lung cancer, colon cancer, breast cancer, pancreatic cancer, and renal cell carcinoma.