Autologous CD171-specific CAR-CD28 zeta-4-1-BB-EGFRt-expressing T Lymphocytes
autologous cd171-specific car-cd28 zeta-4-1-bb-egfrt-expressing t lymphocytes
"A preparation of genetically modified autologous human T-lymphocytes transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) specific for the L1 cell adhesion molecule (L1-CAM/CD171) antigen, and the co-stimulatory signaling domains CD28, 4-1BB (CD137) and CD3 zeta, and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon re-infusion into the patient, the autologous L1-CAM-specific CAR-CD28 zeta-4-1-BB-EGFRt-expressing T-lymphocytes are directed to and induce selective toxicity in L1-CAM-expressing tumor cells. L1-CAM, a neuronal cell adhesion molecule and member of the L1 protein family, plays a key role in the development of the nervous system; it is overexpressed in various tumor cell types and is associated with increased chemoresistance, tumor progression, migration and metastasis. Devoid of both ligand-binding domains and tyrosine kinase activity, EGFRt facilitates both the detection of the administered T-cells in vivo and the elimination of the modified T-cells following a cetuximab-induced antibody-dependent cellular cytotoxicity (ADCC) response. The co-stimulatory signaling domains enhance both proliferation of T-cells and antitumor activity."