US 11,957,695 B2
Methods and compositions targeting glucocorticoid signaling for modulating immune responses
Ana Carrizosa Anderson, Boston, MA (US); Asaf Madi, Boston, MA (US); Nandini Acharya, Boston, MA (US); Vijay K. Kuchroo, Boston, MA (US); and Aviv Regev, Cambridge, MA (US)
Assigned to The Broad Institute, Inc., Cambridge, MA (US); Massachusetts Institute of Technology, Cambridge, MA (US); and The Brigham and Women's Hospital, Inc., Boston, MA (US)
Filed by The Broad Institute, Inc., Cambridge, MA (US); Massachusetts Institute of Technology, Cambridge, MA (US); and The Brigham and Women's Hospital, Inc., Boston, MA (US)
Filed on Apr. 26, 2019, as Appl. No. 16/396,461.
Claims priority of provisional application 62/663,251, filed on Apr. 26, 2018.
Claims priority of provisional application 62/663,520, filed on Apr. 27, 2018.
Prior Publication US 2019/0365781 A1, Dec. 5, 2019
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/573 (2006.01); A61K 35/17 (2015.01); A61K 38/20 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01)
CPC A61K 31/573 (2013.01) [A61K 35/17 (2013.01); A61K 38/20 (2013.01); A61P 35/00 (2018.01); A61K 45/06 (2013.01)] 12 Claims
 
1. A method of treating melanoma by reducing T cell dysfunction in a subject in need thereof comprising:
administering to the subject one or more doses of metyrapone capable of reducing glucocorticoid signaling in the tumor microenvironment,
wherein a dysfunctional immune state in the subject is decreased when glucocorticoid signaling is reduced,
whereby a tumor specific immune response is enhanced.
 
5. A method of treating colon cancer by reducing T cell dysfunction in a subject in need thereof comprising:
administering to the subject one or more doses of metyrapone capable of reducing glucocorticoid signaling in the tumor microenvironment,
wherein a dysfunctional immune state in the subject is decreased when glucocorticoid signaling is reduced,
whereby a tumor specific immune response is enhanced.
 
9. A method of treating stomach cancer by reducing T cell dysfunction in a subject in need thereof comprising:
administering to the subject one or more doses of metyrapone capable of reducing glucocorticoid signaling in the tumor microenvironment,
wherein a dysfunctional immune state in the subject is decreased when glucocorticoid signaling is reduced,
whereby a tumor specific immune response is enhanced.