US 12,186,376 B2
Methods of treating or preventing cancer with an agent that depletes tregs and a checkpoint inhibitor
William R. Bishai, Baltimore, MD (US); John R. Murphy, Tilghman, MD (US); Drew M. Pardoll, Brookeville, MD (US); Laurene Cheung, Baltimore, MD (US); Juan Fu, Lutherville, MD (US); Pankaj Kumar, New Delhi (IN); Amit Kumar, Baltimore, MD (US); Sadiya Parveen, Baltimore, MD (US); Cynthia Korin Bullen, Baltimore, MD (US); Vijayan Sambasivam, Puducherry (IN); Sumit Siddharth, Baltimore, MD (US); and Dipali Sharma, Baltimore, MD (US)
Assigned to The Johns Hopkins University, Baltimore, MD (US)
Appl. No. 16/978,949
Filed by THE JOHNS HOPKINS UNIVERSITY, Baltimore, MD (US)
PCT Filed Mar. 6, 2019, PCT No. PCT/US2019/020959
§ 371(c)(1), (2) Date Sep. 8, 2020,
PCT Pub. No. WO2019/173478, PCT Pub. Date Sep. 12, 2019.
Claims priority of provisional application 62/639,199, filed on Mar. 6, 2018.
Prior Publication US 2022/0023395 A1, Jan. 27, 2022
Int. Cl. A61K 39/395 (2006.01); A61K 38/20 (2006.01); A61K 38/45 (2006.01); A61P 35/00 (2006.01); C07K 16/28 (2006.01)
CPC A61K 38/45 (2013.01) [A61K 38/2013 (2013.01); A61K 39/3955 (2013.01); A61P 35/00 (2018.01); C07K 16/2818 (2013.01); C12Y 204/02036 (2013.01)] 9 Claims
OG exemplary drawing
 
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.