IP Library › Granted Patent US 12,421,316
Granted Patent B2
US 12,421,316 · App. 17/431,853 · Granted Sep 23, 2025

Bispecific immunotoxins targeting human CD25+CCR4+ tumors and regulatory T-cells

Inventors: Zhirui Wang (Denver, CO); Christene Huang (Denver, CO); David Mathes (Englewood, CO); Elizabeth Pomfret (Cherry Hills Village, CO)
Assignee: The Regents of the University of Colorado, a Body Corporate
C07K16/2866A61K45/06A61P35/00C07K14/34C07K14/55C07K2319/55
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Quick Facts
Patent No.
US 12,421,316
App. No.
17/431,853
Granted
Sep 23, 2025
Kind
B2
Abstract

IL2-CCR4 bispecific immunotoxin, CCR4-IL2 bispecific immunotoxin, and methods of use thereof for treatment of refractory and recurrent human CD25 + and/or CCR4 + cutaneous T cell lymphoma, and other human CD25 + or CCR4 + tumors. The bispecific immunotoxin can be also used for broad cancer treatment via depleting CD25 + or CCR4 + Tregs.

Claims (26)

1. A bispecific immunotoxin comprising:

a first part comprising a toxin;

a second part comprising a human interleukin (IL-2); and

a third part comprising an anti-human CC chemokine Receptor 4 (CCR4) antibody including amino acid sequences SEO ID NOs: 9 and 11, or fragments thereof, the second part being linked to the third part.

2. The bispecific immunotoxin of claim 1 , wherein the toxin is diphtheria toxin or a variant thereof.

3. The bispecific immunotoxin of claim 2 , wherein the second part is linked to the third part by a linker.

4. The bispecific immunotoxin of claim 3 , wherein the first part is linked to the second part.

5. The bispecific immunotoxin of claim 4 , wherein the first part is linked to the second part by a linker.

6. The bispecific immunotoxin of claim 5 comprising amino acids 1-791 of SEQ ID NO:4.

7. The bispecific immunotoxin of claim 3 , wherein the first part is linked to the third part.

8. The bispecific immunotoxin of claim 7 , wherein the first part is linked to the third part by a linker.

9. The bispecific immunotoxin of claim 8 comprising amino acids 1-791 of SEQ ID NO:2.

10. A pharmaceutical composition comprising the bispecific immunotoxin of claim 1 , and a physiologically acceptable carrier.

11. A nucleic acid encoding the bispecific immunotoxin of claim 1 .

12. The nucleic acid of claim 11 , wherein the nucleic acid is a codon-optimized nucleic acid molecule optimized for expression in a methylotropic yeast.

13. A vector comprising the nucleic acid molecule of claim 12 .

14. A host cell expressing the nucleic acid molecule of claim 12 .

15. The host cell of claim 14 , wherein the host cell is a methylotropic yeast.

16. A method of producing a IL2-CCR4 bispecific immunotoxin, the method comprising:

expressing a codon-optimized nucleic acid molecule encoding the bispecific immunotoxin of claim 1 in a methylotropic yeast; and

purifying the IL2-CCR4 bispecific immunotoxin,

thereby producing the IL2-CCR4 bispecific immunotoxin.

17. A method of treating a subject who has a cancer, the method comprising administering to the subject a therapeutically effective amount of the bispecific immunotoxin of claim 1 , wherein the cancer is CD25+ or COR4+, and the treating increases the resistance of the subject to further development an existing cancer, eliminates or at least control the existing cancer, and/or reduces the severity of the existing cancer.

18. The method of claim 17 , further comprising administering an immunotherapy to the subject.

19. The method of claim 17 , wherein the cancer is selected from a group of CCR4+ and/or CD25+ tumors.

20. A method of depleting CD25-expressing regulatory T cells in a subject, the method comprising administering to the subject an effective amount of the bispecific immunotoxin of claim 1 .

Continuity (2)
Provisional Application 62807676 · Feb 19, 2019
Related Publication 20220127368A1 · Apr 28, 2022
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