Advantages:
- SHIP-1 as a new molecular target to improve anti-tumor immunity and enhance immune checkpoint immunotherapy responses
- SHIP-1 agonists API and K306 as therapeutics for treating pancreatic cancer
- Combination treatment of a SHIP-1 agonist with a checkpoint inhibitor synergistically reduces tumor burden
Summary:
Portfolio includes two technologies: USF Tech ID# 23T187, 23T188
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with African American (AA) patients having a higher incidence and mortality compared to European American (EA) patients. PDAC is associated with the expansion of anti-tumor immunity that impedes the effectiveness of immunotherapy. Tumor associated immunosuppressive macrophages (M2 TAM) contribute to metastasis and resistance to chemotherapy and immunotherapy.
Our researchers discovered that Src-homology inositol phosphatase-1 (SHIP-1) expression, a master regulator of macrophage development, is important for the repolarization of tumor associated immunosuppressive macrophages (M2 TAM) into tumoricidal macrophages (M1 TAM). They identified that SHIP-1 agonists, bioflavonoid apigenin (API) and K306, reprogrammed M2 TAM into M1 TAM and reduced tumor burden, particularly a burden in AA patients. Administration of a SHIP-agonist in combination with a checkpoint inhibitor such as PD-L1 inhibitor was found to act synergistically to reduce tumor burden. This research highlights SHIP-1 as a biomarker and new molecular target to improve anti-tumor immunity, leading to the development of a novel adjuvant therapies that can enhance the treatment of all PDAC while reducing health disparity gap of African Americans with PDAC.
K306 treatment repolarizes M2 TAM into M1 TAM from African American (AA) to European American (EA) PDAC patients. Flow Cytometry analysis of serum from AA and EA PDAC patients incubated with human differentiated THP-1 macrophages.
Desired Partnerships:
- License
- Sponsored Research
- Co-Development