Treatment of CD47+ disease cells with SIRPα-Fc fusions
CD47+ disease cells, such as CD47+ cancer cells, are treated with an agent that blocks signalling via the SIRPα/CD47 axis. The agent is a human SIRPα fusion protein that displays negligible CD47 agonism and negligible red blood cell binding. The fusion protein comprises an IgV domain from variant 2 of human SIRPα, and an Fc having effector function. The IgV domain binds human CD47 with an affinity that is at least five fold greater than the affinity of the entire extracellular region of human SIRPα. The fusion protein is at least 5 fold more potent than a counterpart lacking effector function.
1. A human SIRPα fusion protein that inhibits the growth and/or proliferation of a CD47+ disease cell, wherein the SIRPα fusion protein comprises SEQ ID NO. 26.
2. The human SIRPα fusion of claim 1 , wherein the human SIRPα fusion protein consists of SEQ ID NO. 26.
3. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an amount of a fusion protein according to claim 1 effective to inhibit the growth or proliferation of a CD47+ disease cell.
4. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an amount of a fusion protein according to claim 2 effective to inhibit the growth or proliferation of a CD47+ disease cell.
5. A polypeptide comprising the amino acid sequence of SEQ ID NO: 26, wherein the polypeptide binds CD47.
6. A protein dimer comprised of two polypeptides according to claim 5 , wherein the protein dimer binds CD47.
7. The protein dimer according to claim 6 , wherein the two polypeptides are linked by at least one disulfide bond between Fc components of the polypeptides that comprise the amino acid sequence of SEQ ID NO: 26.
8. The protein dimer according to claim 7 , wherein the amino acid sequence of each of the two polypeptides consists of SEQ ID NO: 26.
9. A composition comprising the polypeptide according to claim 5 and a pharmaceutically acceptable carrier.
10. The composition of claim 9 , further comprising a chemotherapeutic agent or a radiotherapeutic agent.
11. A composition comprising the protein dimer according to claim 6 and a pharmaceutically acceptable carrier.
12. The composition of claim 11 , further comprising a chemotherapeutic agent or a radiotherapeutic agent.
13. The polypeptide according to claim 5 conjugated to a chemotherapeutic agent or a radiotherapeutic agent.
14. The protein dimer according to claim 6 conjugated to a chemothereapeutic agent or a radiotherapeutic agent.