Definition

A preparation of genetically modified autologous T cells transduced with a replication incompetent, self-inactivating (SIN) lentiviral vector expressing a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) CD123 (interleukin-3 receptor alpha chain or IL3RA) and linked to the CD28 co-stimulatory signaling domain fused to CD3 zeta, and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, the autologous CD123CAR-CD28-CD3zeta-EGFRt-expressing T lymphocytes MB-102 are directed to and induce selective toxicity in CD123-expressing tumor cells. CD123, a subunit of the heterodimeric interleukin-3-receptor (IL-3R), is normally expressed on committed blood progenitor cells in the bone marrow; its overexpression is associated with increased leukemic cell proliferation and aggressiveness. Devoid of both ligand binding domains and tyrosine kinase activity, EGFRt both facilitates detection of the administered T cells in vivo and can promote elimination of those cells following a cetuximab-induced antibody-dependent cellular cytotoxicity (ADCC) response.