CRISPR-Cas9-engineered TGFbRII-deleted anti-EGFR CAR T cells

A preparation of human T lymphocytes genetically engineered to express an anti-epidermal growth factor receptor (EGFR) chimeric antigen receptor (CAR) gene and gene-edited with the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 nuclease complex to disrupt expression of transforming growth factor-beta receptor II (TGFbRII), with potential immunostimulatory and antineoplastic activities. Upon administration, the CRISPR-Cas9 engineered TGFbRII-deleted anti-EGFR CAR T cells target and bind to the EGFR antigen on tumor cell surfaces; subsequently, EGFR-expressing tumor cells may be lysed. EGFR, overexpressed by a variety of cancer cell types, plays a key role in tumor cell proliferation, tumor angiogenesis and radio- and chemoresistance. 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.