Cancer and Aging: A Novel Therapeutic Platform for Targeting Senescence
Session Number
3
Advisor(s)
Dr. VK Gadi, Manali Patwardhan, Dr. Maria Jose Godoy, Eric Gauchat
Location
B116
Discipline
Medical and Health Sciences
Start Date
15-4-2026 2:15 PM
End Date
15-4-2026 3:00 PM
Abstract
Cellular senescence has been identified as a hallmark in cancer patients, as well as age-related comorbidities from accumulation of senescent cells. Growing evidence suggests that senescent cells trigger neighboring cells to become cancerous, migrate, prompt cells to re-enter the cell cycle, and activate cancer stem cells, ultimately promoting tumor survival. However, senescent cells have a vulnerability; they upregulate a certain surface marker called Urokinase plasminogen activator receptor (uPAR) which can be targeted. To develop an anti-uPAR therapy, this project uses surface engineering (SE) to modify Natural Killer (NK) immune cells with custom recombinant protein derived from natural ligand (uPA-ATF) of uPAR. We hypothesize SE NK cells to have higher cytotoxicity towards uPAR expressing cancer cells as compared to the non-engineered (naked) NK cells. To test this, we utilized luciferase-expressing mouse 4T1 breast tumor cells as they inherently express uPAR. The SE and Naked NK cells were placed in co-culture with 4T1 cells for 24 hours. A 5:1 ratio of NK to 4T1 cells was tested. Results indicate that SE NK cells showed higher cytotoxicity than Naked NK cells. This study provides a strong foundation for future studies that investigate precise targeting of senescent cells for therapeutic intervention.
Cancer and Aging: A Novel Therapeutic Platform for Targeting Senescence
B116
Cellular senescence has been identified as a hallmark in cancer patients, as well as age-related comorbidities from accumulation of senescent cells. Growing evidence suggests that senescent cells trigger neighboring cells to become cancerous, migrate, prompt cells to re-enter the cell cycle, and activate cancer stem cells, ultimately promoting tumor survival. However, senescent cells have a vulnerability; they upregulate a certain surface marker called Urokinase plasminogen activator receptor (uPAR) which can be targeted. To develop an anti-uPAR therapy, this project uses surface engineering (SE) to modify Natural Killer (NK) immune cells with custom recombinant protein derived from natural ligand (uPA-ATF) of uPAR. We hypothesize SE NK cells to have higher cytotoxicity towards uPAR expressing cancer cells as compared to the non-engineered (naked) NK cells. To test this, we utilized luciferase-expressing mouse 4T1 breast tumor cells as they inherently express uPAR. The SE and Naked NK cells were placed in co-culture with 4T1 cells for 24 hours. A 5:1 ratio of NK to 4T1 cells was tested. Results indicate that SE NK cells showed higher cytotoxicity than Naked NK cells. This study provides a strong foundation for future studies that investigate precise targeting of senescent cells for therapeutic intervention.