Development of UR238, the First Small-Molecule Inhibitor of HE4 for Treatment of Ovarian Cancer
Abstract
Epithelial Ovarian Cancer (EOC) is the most lethal gynecologic malignancy that women face. Novel targeted therapies for the treatment of EOC are urgently needed. This study aimed to develop the first-in-field novel therapeutic, UR238, designed to target the HE4 protein that is overexpressed in EOC and other HE4 overexpressing cancers. The Rationale for this project stemmed from our ongoing and published research that shows HE4 overexpression in tumors leads chemo-resistance and decreased survival for patients with EOC. Our research also shows that HE4 overexpression promotes expression of the immune checkpoint inhibitor ligand PD-L1 on tumor cells and on tumor associated macrophages, reduces CD8+T cell infiltration into the tumor microenvironment and induces an immune suppressive myeloid switch enriching the environment with immune suppressive M2 macrophages. Each one of these effects assists the tumor in evading the host immune system. The development of UR238 targeting HE4 will mitigate HE4 orchestrated immune evasion in EOC and will introduce a new class of therapeutics to treat EOC. Approximately 80% of patients with EOC tumors overexpress HE4 and these patients may receive clinical benefits from UR238. In addition, patients with endometrioid and serous endometrial cancers along with pancreatic and lung cancer patients also have tumors that overexpress HE4 and will likely benefit from UR238 targeted therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2023
- Accession Number
- AD1227509
Entities
People
- Richard G. Moore
Organizations
- University of Rochester