Treatment of cancer with dual targeting of CD47 and EGFR
Methods are provided for targeting cells for depletion, including without limitation cancer cells, in a regimen comprising contacting the targeted cells with a combination of agents, including (i) an agent that blockades CD47 activity; and (ii) an antibody that specifically binds to EGFR. In some embodiments the cancer cells have a mutated form of one or more of KRAS, NRAS or BRAF. The level of depletion of the targeted cell is enhanced relative to a regimen in which a single agent is used; and the effect may be synergistic relative to a regimen in which a single agent is used.
1. A method of targeting EGFR-expressing colorectal carcinoma cells comprising an activating mutation in KRAS for immunodepletion, the method comprising:
testing the EGFR-expressing colorectal carcinoma cells for the presence of an activating mutation in one or more of KRAS, NRAS and BRAF;
selecting for treatment the colorectal carcinoma cells in which one or more of said activating mutations is present;
contacting a population of the colorectal carcinoma cells in an individual mammal in vivo with (i) an agent that blockades CD47 activity selected from an antibody that binds to CD47; an antibody that binds to SIRPα; a soluble SIRPα-binding CD47 fragment; and a soluble CD47-binding SIRPα fragment; and (ii) an antibody that specifically binds to epidermal growth factor receptor; in a dose effective to increase immunodepletion of the EGFR-expressing colorectal carcinoma cells by phagocytic cells.
2. The method of claim 1 , wherein the treatment provides for increased overall survival of the individual.
3. The method of claim 1 , wherein depletion of the target cells is enhanced relative to the depletion observed with a monotherapy of (i) an agent that blockades CD47 activity; or (ii) an anti-EGFR antibody.
4. The method of claim 1 , wherein the agent that blockades CD47 activity is an anti-CD47 antibody.
5. The method of claim 4 , wherein the anti-CD47 antibody comprises an IgG4 Fc region.
6. The method according to claim 1 , wherein said mammal is a mouse.
7. The method according to claim 1 , wherein said mammal is a human.
8. The method of claim 1 , wherein the antibody that specifically binds to epidermal growth factor receptor is selected from the group consisting of cetuximab, panitumumab, nimotuzumab, zalutumumab and matuzumab.
9. The method of claim 1 , wherein the antibody that specifically binds to epidermal growth factor receptor is other than an antibody conjugated to a drug.