Treatment of cancer with dual targeting of CD47 and EGFR

Patent metadata

Field	Value
Publication number	US-10344094-B2
Application number	US-201615373150-A
Country	US
Kind code	B2
Filing date	Dec 8, 2016
Priority date	Dec 11, 2015
Publication date	Jul 9, 2019
Grant date	Jul 9, 2019

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Univ Leland Stanford Junior

Inventors

• Weissman Irving L
• Willingham Stephen
• Ho Doris Po Yi
• Dalerba Piero D
• McKenna Kelly Marie
• Volkmer Jens-Peter

Classifications

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• A61K2039/507

  Comprising a combination of two or more separate antibodies · CPC title

• C07K16/2839

  against the integrin superfamily · CPC title