Definition

Autologous human T lymphocytes that are genetically engineered to express a chimeric antigen receptor (CAR) containing an anti-T-cell receptor beta constant 1 (TRBC1; T-cell receptor beta-1 chain C region) single chain variable fragment (scFv) and the co-stimulatory domain 4-1BB (CD137) coupled to the zeta chain of the TCR/CD3 complex (CD3-zeta), with potential immunostimulating and antineoplastic activities. Upon administration, anti-TRBC1-CAR-CD3zeta-4-1BB-RQR8-expressing autologous T lymphocytes AUTO4 targets and binds to the TRBC1 expressed on tumor cell surfaces. Subsequently, TRBC1-expressing tumor cells are lysed. In addition, AUTO4 carries the universal RQR8 safety “off” switch, which allows selective removal of the T-cells through both complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) following administration of rituximab if unacceptable side-effects occur.