Tuning the SUPRA CAR to differentiate high/low Her2 levels
OA Version
Citation
Abstract
On-target, off-tumor toxicity has been a major challenge for chimeric antigen receptor (CAR) T cells to clinically treat solid tumors. This is due to conventional CAR T cells poorly discriminating between high and low tumor associated antigen densities, causing them to attack both cancer and healthy cells. Her2 is a tumor associated antigen where it is minimally expressed in healthy cells and overexpressed in cancer cells of Her2 positive cancer patients. Previous case reports demonstrate that targeting Her2 with conventional ɑ-Her2-CAR could be fatal. To reduce the risk of on-target, off-tumor toxicity, an ultrasensitive CAR T cell platform that highly activates against high antigen density and minimally activates against low antigen density is in need. The Wong lab has developed the split, universal and programmable (SUPRA) CAR system for a safer and more effective CAR. Composed of a universal receptor and an exogenous scFv protein, this split CAR allows safe, effective, and flexible control over T cell activity due to its various tunable components. This thesis aims to demonstrate that the SUPRA CAR can differentiate high and low Her2 densities more than that of a conventional ɑ-Her2-CAR.