Definition

A preparation of autologous T lymphocytes engineered to co-express two chimeric antigen receptors (CARs) specific for epidermal growth factor receptor (EGFR) epitope 806 and interleukin-13 receptor alpha 2 (IL13Ra2), with potential immunostimulating and antineoplastic activities. After isolation, transduction, expansion and reintroduction into the patient, the autologous anti-EGFR/anti-IL13Ra2 CAR T cells are directed to, bind to, and induce selective toxicity in EGFR deletion mutation variant III (EGFRvIII)-expressing and IL13Ra2-expressing tumor cells. EGFRvIII, an in-frame deletion of exons 2-7 in the EGFR gene, is overexpressed by a variety of cancer cell types but absent in normal, healthy cells. It plays a key role in tumor cell proliferation, tumor angiogenesis and resistance to both radio- and chemotherapy. IL13Ra2, a cancer-associated receptor, is overexpressed by a variety of tumor cell types including glioblastoma multiforme (GBM); it is associated with increased invasiveness of tumor cells. The binding of IL13Ra2 to EGFRvIII upregulates the tyrosine kinase activity of EGFRvIII and promotes tumor cell proliferation.