Autologous TGFbRII-knockout Anti-interleukin-13 Receptor Alpha 2 CAR T-cells
autologous tgfbrii-knockout anti-interleukin-13 receptor alpha 2 car t-cells
A preparation of autologous T-lymphocytes engineered to express a chimeric antigen receptor (CAR) specific for interleukin-13 receptor alpha 2 (IL13Ra2), and to knock out the expression of transforming growth factor-beta receptor II (TGFbRII), with potential immunostimulating and antineoplastic activities. Upon administration, autologous TGFbRII-KO anti-IL13Ra2 CAR T-cells target and bind to IL13Ra2 expressed on the surface of tumor cells. This induces selective toxicity in tumor cells expressing IL13Ra2. IL13Ra2, a cancer-associated receptor, is overexpressed by a variety of tumor cell types including glioblastoma multiforme (GBM); it is associated with increased invasiveness of tumor cells. By knocking out the expression of TGFbRII, the immunosuppressive cytokine TGF-beta is unable to bind to the T-cells and prevent the activation of the T-cells. TGF-beta contributes to the immunosuppressive nature of the tumor microenvironment (TME), and plays a key role in promoting tumor initiation, metastasis, and suppressing anti-tumor immunity.