Che-Hsing “Kevin” Li, MD
Protein-free Drug Inducible Transgene Expression Platform in CAR T Cells
Abstract
Interleukin-15 (IL15)-armored glypican-3 (GPC3)-targeting chimeric antigen receptor (CAR) T cells can induce responses in patients with hepatocellular carcinoma (HCC); however, patients experiencing severe toxicities, required the activation of iC9 safety switch to eliminate the engineered cells. To avoid elimination of CAR T cells, we now employed a tetracycline (Tc)-inducible transgene expression platform, pA regulator (PAR), in CAR T cells. T cells are transduced by a lentiviral vector enabling the constitutive expression of the GPC3-CAR and the controllable PAR cassette. Our preliminary data demonstrates that PAR controlled dsGFP was significantly induced at 2 µg/mL Tc (compatible with Tc human oral dosing) in GPC3-CAR T cells. I hypothesize that PAR controlled IL15 signaling will safely improve antitumor activity of GPC3-CAR T. I will determine PAR controlled GPC3-CAR T safety, expansion, persistence (Aim 1) as well as polyfunctionality and antitumor activity against HCC (Aim 2).
Receiving this fellowship from the PhRMA Foundation is a significant catalyst for our research. It empowers us to push the boundaries of CAR-T cell engineering to better serve patients with solid tumors while supporting my personal journey toward bridging the gap between laboratory innovation and clinical care.
