autologous anti-B7-H3/CD19 CAR T cells SCRI-CARB7H3(s)x19

A preparation of autologous CD4+ and CD8+ T lymphocytes lentivirally transduced to express a chimeric antigen receptor (CAR) targeting the immunoregulatory protein B7-homologue 3 (B7-H3, CD276) and the tumor-associated antigen (TAA) CD19, and containing, as of yet undisclosed co-stimulatory signaling domains, and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon administration, anti-B7-H3/CD19 CAR T cells target and bind to both B7-H3 on T cells and CD19 on tumor cells. This crosslinks T cells and tumor cells, and induces selective toxicity in B7-H3/CD19-expressing tumor 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 promotes the activation of T cells. CD19, a transmembrane phosphoglycoprotein expressed on the surface of cells in the B lineage, are often overexpressed on malignant B cells. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt both facilitates in vivo detection of the administered, transduced T cells and can promote elimination of those cells through a cetuximab-induced antibody dependent cellular cytotoxicity (ADCC) response.