anti-EGFRvIII-CAR-CD3/EGFR BiTE-transduced autologous T lymphocytes CARv3-TEAM-E

A preparation of autologous human T lymphocytes transduced with a CARv3-TEAM-E lentiviral vector encoding for an anti-epidermal growth factor receptor (EGFR) variant III (EGFRvIII) mutant chimeric T-cell receptor (chimeric antigen receptor or CAR) and a T-cell-engaging antibody molecule (TEAM) which comprises a bispecific T-cell engager (BiTE) against EGFR and the T-cell signaling domain CD3, with potential immunostimulatory and antineoplastic activities. Upon administration via Ommaya reservoir of the anti-EGFRvIII CAR-CD3/EGFR BiTE-transduced autologous T lymphocytes CARv3-TEAM-E, the lymphocytes bind to the EGFRvIII antigen on tumor cell surfaces and the BiTE binds to CD3 on bystander T cells; thereby killing EGFRvIII-expressing tumor cells through the administered CAR-T cells and wild-type (WT) EGFR-expressing tumor cells by bystander T cells, respectively. EGFRvIII, an in-frame deletion of exons 2-7 in the EGFR gene, is overexpressed by a variety of cancer cell types and absent in normal, healthy cells; it plays a key role in tumor cell proliferation, tumor angiogenesis and radio- and chemoresistance.