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

Categories: “Cancer Therapeutics“

Reference #: 2021-018

OTC Contact: Ruchika Nijhara, Ph.D., MBA, CLP (Directory Information | Send a Message)

Invention

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 and in vitro culture 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.

Applications

• 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

Advantages

• Potential to be expanded to additional immune cell types, such as T cells
• Ability to visualize and quantify human NK cell migration and extravasation in vivo

Stage of Development

The inventors have compelling data to show that inhibition of FAP expression on NK cells blocks their migration. Studies are ongoing to knock out FAP in vivo.

Patent Status

Patent application has been filed. PCT/US2022/014077

Inventors

Louis M Weiner

Allison Fitzgerald