autologous B7-H3/EGFR806/HER2/IL13-zetakine CAR-expressing CD4+/CD8+ T cells SC-CAR4BRAIN

A preparation of autologous CD4+ and CD8+ T lymphocytes transduced with a lentiviral vector to express four chimeric antigen receptors (CARs) targeting the immunoregulatory protein B7-homologue 3 (B7-H3, CD276), epidermal growth factor receptor (EGFR) mAb806 epitope, human epidermal growth factor 2 (HER2; ErbB2; HER-2), and interleukin-13 receptor alpha 2 (IL13Ra2), with potential immunostimulating and antineoplastic activities. Upon administration, autologous B7-H3/EGFR806/HER2/IL13-zetakine CAR-expressing CD4+/CD8+ T cells SC-CAR4BRAIN target and bind to tumor cells that express B7-H3, EGFR mAb806 epitope, HER2 and IL13Ra2, thereby inducing selective toxicity in these cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells. It is a negative regulator of T-cell activation and its overexpression plays a key role in tumor cell invasion and metastasis. EGFR, overexpressed by a variety of cancer cell types, plays a key role in tumor cell proliferation, tumor angiogenesis and radio- and chemoresistance. EGFR806 CAR specifically targets abnormal conformational states of EGFR, including EGFR deletion mutation variant III (EGFRvIII), and activating mutations, with lower affinity for wild-type EGFR. HER2 is overexpressed in a variety of cancer cell types and is associated with increased tumor cell proliferation. 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.