autologous CD5KO anti-CD5 CAR 4-1BB-expressing T lymphocytes and autologous CD5KO T lymphocytes

A dual-population preparation of autologous T lymphocytes in which the tumor-associated antigen (TAA) CD5 is knocked out (CD5KO) and is genetically modified to express a chimeric antigen receptor (CAR) specific for CD5 and coupled to the co-stimulatory molecule 4-1BB (CD137), and autologous CD5KO normal untransduced T lymphocytes, with potential immunomodulating and antineoplastic activities. Upon administration of autologous CD5KO anti-CD5 CAR 4-1BB-expressing T lymphocytes and autologous CD5KO T lymphocytes, the autologous CD5KO anti-CD5 CAR 4-1BB-expressing T lymphocytes specifically recognize and kill CD5-expressing tumor cells. CD5 is a T-cell surface glycoprotein expressed on the surface of normal T cells and overexpressed on various B- and T-cell malignancies. CD5 KO in the CART5 cells prevents CART fratricide and enhances CAR-T cell function. The CD5KO normal T cells allow for T-cell reconstitution and may mitigate T-cell toxicity.