Modulation of Fibroblast Activation Protein (FAP) Activity on Natural Killer (NK) and T-Cells for Cancer Therapy

OVERVIEW

In cancer, patients with high content and activation of natural killer (NK) tumor cells have better survival and response to immunotherapy. However, therapies based on NK cells currently have limitations regarding NK cells honing to and/or infiltration into solid tumors. This forefront technology addresses cancer treatment through the administration of modified immune cells that overexpress fibroblast activation protein (“FAP”). Novel in vivo 3D zebrafish andin vitroculture models was used to demonstrate that FAP regulates NK cell migration, extravasation, and infiltration into tumors and enhances their anti-tumor activity, and provides a potential therapy to improve cancer patient outcomes.

BACKGROUND

Currently, available chimeric antigen receptor (CAR) T cells and NK cells have limited success in eradicating solid tumors because they have a poor ability to infiltrate the dense tumor microenvironment. Georgetown researchers’ findings demonstrate that FAP activity can be manipulated to alter immune cell migration. Through this innovative approach, NK cells or (CAR) NK cells could be engineered to overexpress FAP, enhancing their ability to infiltrate solid tumors and lyse malignant cells. This technique can be expanded to additional immune cell types, such as T cells.

Benefit

• Potential to be expanded to additional immune cell types, such as T cells.

• Ability to visualize and quantify human NK cell migration and extravasationin vivo.

Market Application

• Promising therapeutic target in cancer.

• Cancer treatment through the administration of modified immune cells.

• Potential use to treat any solid malignancy.

• Ability to further engineer cells to express chemokine receptors to facilitate tumor homing.

Publications

• Patent application has been filed. PCT/US2022/014077
• Understanding and Targeting Natural Killer Cell-Cancer-Associated Fibroblast Interactions in Pancreatic Ductal Adenocarcinoma. Cancers (Basel). 2021 Jan 22;13(3):405. doi: 10.3390/cancers13030405. PMID: 33499238; PMCID: PMC7865209.
• The role of fibroblast activation protein in health and malignancy. Cancer Metastasis Rev. 2020 Sep;39(3):783-803. doi: 10.1007/s10555-020-09909-3. PMID: 32601975; PMCID: PMC7487063.
• Fibroblast activation protein regulates natural killer cell migration, extravasation and tumor infiltration.bioRxiv2021.02.03.429622;doi:https://doi.org/10.1101/2021.02.03.429622