CD19R(EQ)-CD28-CD3zeta-EGFRt-expressing T lymphocytes

A preparation of genetically modified T cells transduced expressing a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19 and containing the CD28 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, CD19R(EQ)-CD28-CD3zeta-EGFRt-expressing T lymphocytes are directed to CD19-expressing tumor cells, thereby inducing a selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Devoid of both ligand binding domains and tyrosine kinase activity, EGFRt both facilitates in vivo detection of the administered T cells and can promote elimination of those cells upon a cetuximab-induced antibody dependent cellular cytotoxicity (ADCC) response. The costimulatory signaling domain enhances proliferation of T-cells and antitumor activity. CD19R(EQ) contains two-point mutations in the immunoglobulin (Ig) G4 Fc spacer region, thereby preventing recognition of the CAR by Fc gamma receptors (FcgammaRs).