IP Library Granted Patent US 11,071,777
Granted Patent B2
US 11,071,777 · App. 15/956,909 · Granted Jul 27, 2021

Tetanus toxoid and CCL3 improve DC vaccines

Inventors: John H. Sampson (Durham, NC); Duane A. Mitchell (Gainesville, FL); Kristen A. Batich (Durham, NC); Michael D. Gunn (Durham, NC)
Assignee: Duke University
A61K39/08A61K38/195A61K39/0011A61K39/05A61K39/092A61K39/102A61K39/12A61K39/39A61K49/0008A61K49/06C07K14/285C07K14/3156C07K14/33C07K14/34C07K14/4748C07K14/523C12N7/00A61K2039/5154A61K2039/5158A61K2039/53A61K2039/54A61K2039/545A61K2039/55544A61K2039/58A61K2039/585A61K2039/70C07K2319/55C12N2710/16134C12N2710/16171
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Quick Facts
Patent No.
US 11,071,777
App. No.
15/956,909
Granted
Jul 27, 2021
Kind
B2
Abstract

Pre-conditioning a vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumor antigen-specific DC vaccines. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumor growth in a manner dependent on the chemokines CCL3 and CCL21 and Td-activated CD4 + T cells. Interference with any component of this axis markedly reduced Td-mediated DC migration and antitumor responses. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen represents a viable strategy to increase DC homing to lymph nodes and improve antitumor immunotherapy.

Claims (16)

1. A kit comprising a container comprising a tetanus toxoid, a diphtheria toxoid and either a CMV antigen or a RNA encoding a CMV antigen.

2. The kit of claim 1 , wherein said kit further comprises chemokine CCL3.

3. The kit of claim 1 , wherein said CMV antigen is pp65.

4. The kit of claim 1 , wherein said kit comprises a RNA encoding said CMV antigen.

5. The kit of claim 4 , wherein said CMV antigen is pp65.

6. The kit of claim 3 , wherein said kit further comprises chemokine CCL3.

7. The kit of claim 4 , wherein said kit further comprises chemokine CCL3.

8. The kit of claim 5 , wherein said kit further comprises chemokine CCL3.

9. The kit of claim 1 , wherein said kit further comprises an antigen pulsed dendritic cell vaccine.

10. The kit of claim 9 , wherein said dendritic cell vaccine was pulsed with a CMV antigen.

11. The kit of claim 10 , wherein said dendritic cell vaccine was pulsed with a CMV integument protein pp65 RNA.

12. The kit of claim 10 , wherein said dendritic cell vaccine was pulsed with a CMV integument protein pp65.

13. The kit of claim 9 , wherein said kit further comprises chemokine CCL3.

14. The kit of claim 10 , wherein said kit further comprises chemokine CCL3.

15. The kit of claim 11 , wherein said kit further comprises chemokine CCL3.

16. The kit of claim 12 , wherein said kit further comprises chemokine CCL3.

Continuity (3)
Division 15036878
Provisional Application 61904250 · Nov 14, 2013
Related Publication 20180236054A1 · Aug 23, 2018