Abstract: The invention relates to compositions and methods for inhibiting Krüppel-like Factor 10 (KLF10) for modulation of T regulatory cells and cancer immunotherapy.
Type:
Grant
Filed:
October 28, 2016
Date of Patent:
March 8, 2022
Assignees:
The Brigham and Women's Hospital, Inc., Beth Isreal Deaconess Medical Center, Inc.
Abstract: The present disclosure describes how all-retinoic acid (ATRA) binds and inhibits Pin1 activity and induces degradation of the activated Pin1 monomer selectively in cancer cells. Identification of the binding mechanism of ATRA with Pin1 confirm ATRA binding specificity to Pin1 residues in the PPIase active site, thus demonstrating that drug-induced Pin1 ablation has potent anticancer activity, such as in acute promyelocytic leukemia (APL), by inducing PML-RARa degradation, as well as against other types of cancer and diseases that are associated with Pin1 overexpression, such as aggressive triple negative breast cancer, lupus, asthma, cocaine addiction, among others, due to their unique ability to simultaneously block numerous cancer-driving pathways, with relatively lower toxicity. The present disclosure also provides a rationale for developing sustained released ATRA-containing formulations.
Type:
Grant
Filed:
July 16, 2015
Date of Patent:
May 15, 2018
Assignee:
Beth Isreal Deaconess Medical Center, Inc.
Abstract: In particular embodiments, the present invention provides methods of inhibiting smooth muscle cell responses and methods of treating or preventing vascular proliferative disease caused by smooth muscle cell migration and proliferation. More specifically, smooth muscle cell responses are inhibited by introducing an agent into smooth muscle cells, wherein the agent inhibits an activity of one or more members of the myristoylated alanine-rich C kinase substrate (MARCKS) family of proteins. The invention also provides methods of inhibiting expression of one or more genes encoding a member of the MARCKS family of proteins in a cell.
Type:
Grant
Filed:
August 3, 2007
Date of Patent:
February 21, 2012
Assignee:
Beth Isreal Deaconess Medical Center, Inc.
Inventors:
Thomas S. Monahan, Frank W. LoGerfo, Nicholas D. Andersen