allogeneic anti-CD20/CD22 universal CAR-expressing T lymphocytes UCART20x22

A preparation of allogeneic, off-the-shelf (OTS), universal transcription activator-like effector nuclease (TALEN)-engineered T lymphocytes that have been genetically modified to express chimeric antigen receptors (CARs) specific for the tumor-associated antigens (TAAs) cluster of differentiation 20 (CD20) and CD22, with potential immunostimulating and antineoplastic activities. Using TALEN technology, the T-cell receptor (TCR) alpha chain (TRAC) and CD52 genes are inactivated. Upon administration, the allogeneic anti-CD20/CD22 universal CAR-expressing T lymphocytes UCART20x22 specifically recognize and induce selective toxicity in CD20- and CD22-expressing tumor cells. CD20 and CD22 are overexpressed in certain hematologic malignancies. Inactivation of the CD52 gene makes the CAR-T cells UCART20x22 resistant to anti-CD52 monoclonal antibody treatment that is used during preconditioning regimen to enhance the expansion and persistence of the CAR-T cells. The knockout of TRAC eliminates TCR expression and is intended to abrogate the potential induction of graft-versus-host disease (GvHD) by the CAR-T cells.