The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Dec. 22, 2020

Filed:

Jul. 13, 2015
Applicant:

The Johns Hopkins University, Baltimore, MD (US);

Inventors:

Shibin Zhou, Owings Mills, MD (US);

Bert Vogelstein, Baltimore, MD (US);

Kenneth W. Kinzler, Baltimore, MD (US);

KiBem Kim, Lutherville, MD (US);

Assignee:

The Johns Hopkins University, Baltimore, MD (US);

Attorney:
Primary Examiner:
Int. Cl.
CPC ...
A61K 39/395 (2006.01); A61K 31/437 (2006.01); A61K 31/00 (2006.01); A61K 31/706 (2006.01); A61K 31/4406 (2006.01); C07K 16/28 (2006.01); A61K 45/06 (2006.01); A61K 35/742 (2015.01); A61K 39/00 (2006.01);
U.S. Cl.
CPC ...
A61K 39/39558 (2013.01); A61K 31/437 (2013.01); A61K 31/4406 (2013.01); A61K 31/706 (2013.01); A61K 35/742 (2013.01); A61K 39/3955 (2013.01); A61K 45/06 (2013.01); C07K 16/2818 (2013.01); A61K 2039/505 (2013.01); C07K 2317/34 (2013.01); C07K 2317/92 (2013.01);
Abstract

Impressive responses have been observed in patients treated with checkpoint inhibitory anti-PD-1 or anti-CTLA-4 antibodies. However, immunotherapy against poorly immunogenic cancers remains a challenge. Treatment with both anti-PD-1 and anti-CTLA-4 antibodies were unable to eradicate large, modestly immunogenic CT26 tumors or metastatic 4T1 tumors. However, co-treatment with epigenetic modulating drugs and checkpoint inhibitors markedly improved treatment outcomes, curing more than 80% of them. Functional studies revealed that the primary targets of the epigenetic modulators were myeloid-derived suppressor cells (MDSCs). A PI3K-inhibitor that reduced circulating MDSCs also cured 80% of mice with metastatic 4T1 tumors when combined with immune checkpoint inhibitors. Thus, cancers resistant to immune checkpoint blockade can be cured by eliminating MDSCs.


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