IP Library › Granted Patent US 12,186,376
Granted Patent B2
US 12,186,376 · App. 16/978,949 · Granted Jan 7, 2025

Methods of treating or preventing cancer with an agent that depletes tregs and a checkpoint inhibitor

Inventors: William R. Bishai (Baltimore, MD); John R. Murphy (Tilghman, MD); Drew M. Pardoll (Brookeville, MD); Laurene Cheung (Baltimore, MD); Juan Fu (Lutherville, MD); Pankaj Kumar (New Delhi, IN); Amit Kumar (Baltimore, MD); Sadiya Parveen (Baltimore, MD); Cynthia Korin Bullen (Baltimore, MD); Vijayan Sambasivam (Puducherry, IN); Sumit Siddharth (Baltimore, MD); Dipali Sharma (Baltimore, MD)
Assignee: The Johns Hopkins University
A61K38/45A61K38/2013A61K39/3955A61P35/00C07K16/2818C12Y204/02036
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Quick Facts
Patent No.
US 12,186,376
App. No.
16/978,949
Granted
Jan 7, 2025
Kind
B2
Abstract

The present invention is related to a method of treating or preventing cancer in a subject comprising administering to a subject having cancer or prone of getting cancer a first agent that depletes the subject's regulatory T cells (Tregs); followed by administering to the subject a second agent comprising a checkpoint inhibitor.

Claims (18)

1. A method of treating cancer in a subject comprising:

(a) administering to a subject having cancer a first agent that depletes the subject's regulatory T cells (Tregs) comprising a diphtheria toxin fusion protein which comprises a diphtheria toxin fragment A; a diphtheria toxin fragment B; or a combination thereof,

wherein the first agent comprises (i) SEQ ID NO: 58; SEQ ID NO: 15, SEQ ID NO: 43; or a combination thereof or (ii) an expression vector encoding a protein sequence comprising SEQ ID NO: 58; SEQ ID NO: 15, SEQ ID NO: 43; or a combination thereof; followed by

(b) administering to the subject a second agent comprising a checkpoint inhibitor,

wherein the cancer is a Tregs infiltrated cancer,

thereby treating cancer in the subject.

2. The method of claim 1 wherein the cancer is melanoma, breast cancer, colon cancer, renal cell cancer, glioblastoma multiforme, lung cancer or epidermoid carcinoma.

3. The method of claim 1 wherein the diphtheria toxin fusion protein comprises human interleukin sequences.

4. The method of claim 3 wherein the human interleukin sequences consist of an IL-2 protein or functional parts thereof.

5. The method of claim 3 wherein the diphtheria toxin fusion protein, comprising a mutant diphtheria toxin protein, causes reduced vascular leakage as compared to a reference diphtheria toxin fusion protein comprising a wild-type diphtheria toxin protein.

6. The method of claim 1 wherein the checkpoint inhibitor is an anti-CTLA-4 antibody, an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination thereof.

7. The method of claim 1 wherein the checkpoint inhibitor is selected from the group consisting of ipilimumab (anti-CTLA-4), nivolumab (anti-PD-1), pembrolizumab (anti-PD-1), atezolizumab (anti-PD-L1), avelumab (anti-PD-L1), and durvalumab (anti-PD-L1), or a combination thereof.

8. The method of claim 1 wherein the second agent is an anti-PD1 antibody.

9. A method of treating cancer in a subject comprising:

(a) administering to a subject having cancer a first agent that depletes the subject's regulatory T cells (Tregs) comprising a diphtheria toxin fusion protein, wherein the first agent comprises (i) SEQ ID NO: 58; or SEQ ID NO: 43; or (ii) an expression vector encoding a protein sequence comprising SEQ ID NO: 58; or SEQ ID NO: 43; followed by

(b) administering to the subject a second agent comprising a checkpoint inhibitor, wherein the checkpoint inhibitor is an anti-PD-1 antibody,

wherein the cancer is a Tregs infiltrated cancer,

thereby treating cancer in the subject.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 27, 2020
From: MURPHY, JOHN R.; PARVEEN, SADIYA; BULLEN, CYNTHIA KORIN; BISHAI, WILLIAM R.; KUMAR, PANKAJ; KUMAR, AMIT; SAMBASIVAM, VIJAYAN; PARDOLL, DREW M.; CHEUNG, LAURENE; FU, JUAN; SIDDHARTH, SUMIT; SHARMA, DIPALI
To: THE JOHNS HOPKINS UNIVERSITY
Reel/Frame 054184/0473 →
Continuity (2)
Provisional Application 62639199 · Mar 6, 2018
Related Publication 20220023395A1 · Jan 27, 2022
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