autologous anti-PD-L1-armored anti-CD22 CAR T cells

A preparation of autologous T lymphocytes that have been genetically engineered to express a chimeric antigen receptor (CAR) specific for the human tumor-associated antigen (TAA) CD22 and carrying a single-chain variable fragment (scFv) of a monoclonal antibody targeting the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), with potential immunomodulatory and antineoplastic activities. Upon infusion, the autologous anti-PD-L1-armored anti-CD22 CAR T cells target and bind to CD22-expressing tumor cells, thereby inducing selective toxicity in CD22-expressing tumor cells. The scFv moiety binds to PD-L1, blocking the binding of PD-L1 to its receptor programmed cell death 1 (PD-1; cluster of differentiation 279; CD279), thereby preventing PD-1 activation on T lymphocytes. This reverses T-cell inactivation caused by PD-1/PD-L1 signaling and enhances the cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune response against PD-L1-expressing tumor cells. PD-L1 is overexpressed by many human cancer cell types and plays a key role in the downregulation of the immune system and tumor evasion from host immunity. PD-1, found on activated T cells, negatively regulates T-cell activity; it plays a key role in immune evasion and prevents tumor cell lysis. CD22, a cell surface glycoprotein, is expressed on mature B cells and on most malignant B cells.