IP Library › Granted Patent US 12,421,495
Granted Patent B2
US 12,421,495 · App. 17/198,103 · Granted Sep 23, 2025

Compositions and methods for selective phagocytosis of human cancer cells

Inventors: Dennis E. Discher (Philadelphia, PA); Kyle R. Spinler (La Jolla, CA); Cory Alvey (Philadelphia, PA)
Assignee: The Trustees of the University of Pennsylvania
C12N5/0645A61K35/28A61K40/10A61K40/17A61K40/24A61K40/4202A61K40/4204A61K40/4257A61K47/6851A61K49/0041A61K49/0097A61K2035/124A61K2239/31A61K2239/38A61K2239/55C12N2510/00
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Quick Facts
Patent No.
US 12,421,495
App. No.
17/198,103
Granted
Sep 23, 2025
Kind
B2
Abstract

The present invention relates to compositions and methods that provide novel therapies in cancer. The invention includes a phagocytic cell modified with a repressor of signal regulatory protein-alpha (SIRPα) and bound to a targeting antibody to enhance phagocytic activity of the phagocytic cell toward tumor tissue. Methods of enhancing phagocytic activity and treating a tumor are also included.

Claims (18)

1. A method of enhancing phagocytic activity of a phagocytic cell toward tumor tissue in a mammal, the method comprising administering to the mammal an effective amount of a composition comprising a signal regulatory protein-alpha (SIRPα) repressed phagocytic cell bound to a targeting antibody, wherein the effective amount of the composition enhances phagocytic activity and has a therapeutic effect in the mammal, wherein the phagocytic cell is a bone marrow cell.

2. The method of claim 1 , wherein the therapeutic effect comprises tumor tissue shrinkage of at least 60% of the tumor tissue.

3. The method of claim 1 , wherein the phagocytic cell is modified by at least one selected from the group consisting of anti-SIRPα antibody, SIRPα-shRNA, SIRPα -siRNA, SIRPα antagonist, a CRISPR system targeted to SIRPα, and a combination thereof.

4. The method of claim 1 , wherein the phagocytic cell is bound to the targeting antibody through a Fc receptor on the phagocytic cell.

5. The method of claim 1 , wherein the targeting antibody is a tumor specific antibody.

6. The method of claim 1 , wherein the phagocytic cell is administered intravenously to the mammal.

7. The method of claim 1 , wherein the mammal is a human.

8. A method of treating a tumor in a mammal, the method comprising administering to the mammal an effective amount of a composition comprising a signal regulatory protein-alpha (SIRPα) repressed phagocytic cell bound to a targeting antibody, wherein the effective amount of the composition has a therapeutic effect in the mammal, thereby treating the tumor tissue, and wherein the phagocytic cell is a bone marrow cell.

9. The method of claim 8 , wherein the therapeutic effect comprises tumor tissue shrinkage of at least 60% of the tumor tissue.

10. The method of claim 8 , wherein the phagocytic cell is modified by at least one selected from the group consisting of anti-SIRPα antibody, SIRPα-shRNA, SIRPα -siRNA, SIRPα antagonist, a CRISPR system targeted to SIRPα, and a combination thereof.

11. The method of claim 8 , wherein the phagocytic cell is bound to the targeting antibody through a Fc receptor on the phagocytic cell.

12. The method of claim 8 , wherein the targeting antibody is a tumor specific antibody.

13. The method of claim 8 , wherein the phagocytic cell is administered intravenously to the mammal.

14. The method of claim 8 , wherein the mammal is a human.

15. A method of modifying a phagocytic activity to target a specific tissue in a mammal, the method comprising contacting a phagocytic cell with a repressor of signal regulatory protein-alpha (SIRPα) and a targeting antibody, wherein the modified phagocytic cell has enhanced phagocytic activity and a therapeutic effect on the tissue in the mammal, wherein the phagocytic cell is a bone marrow cell.

16. The method of claim 15 , wherein the targeting antibody is a tumor specific antibody.

17. A method of modulating phagocytic activity to target a specific tissue in a mammal, the method comprising administering to the mammal an effective amount of a composition comprising a signal regulatory protein-alpha (SIRPα) repressed bone marrow cell and an opsonin, wherein the effective amount of the composition modulates phagocytic activity and has a therapeutic effect on the tissue in the mammal.

18. A method of treating a tumor in a mammal, the method comprising administering to the mammal an effective amount of a composition comprising a signal regulatory protein-alpha (SIRPα) repressed bone marrow cell and opsonin, thereby treating the tumor tissue.

Continuity (4)
Continuation 15366844 · Dec 1, 2016
Provisional Application 62376712 · Aug 18, 2016
Provisional Application 62261690 · Dec 1, 2015
Related Publication 20210220401A1 · Jul 22, 2021
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