Abstract: The present disclosure provides a chimeric antigen receptor (CAR) immunotherapy for treating a hematologic cancer comprising (a) genetically modifying a population of immune effector cells comprising T cell receptors (TCRs) to stably express at least one CAR, wherein the ectodomain of the CAR specifically binds a cancer antigen; (b) expanding the population of CAR-containing immune effector cells in the presence of one or more cytokines in vitro to achieve a therapeutic dose, wherein the population of CAR-containing immune effector cells exhibits a nonexhausted memory T cell phenotype; and (c) infusing eligible subjects with the CAR-containing immune effector memory T cell phenotype population of cells as needed until the hematologic cancer in the body is destroyed. The intracellular signal transduction domain of the CAR includes 4-1BB, a CD3? T cell activation chain and a genetically engineered TLE3, which can be ectopically expressed.

Abstract: The present disclosure relates to cell therapy methods comprising administering a hematopoietic cell transplant comprising a population of genetically engineered T cells that overexpress PD-L1 and IFN-?2 (??-T cells) to a recipient subject in need thereof, wherein the recipient in need thereof is afflicted with an autoimmune or alloimmune disorder. The genetically engineered population of ??-T cells is characterized by expansion in vitro, persistence in vivo, capacity to infiltrate target tissues; and sustained immune modulatory function. In one application, an administered allogeneic or autologous hematopoietic cell transplant suppresses graft versus host reactivity in a recipient subject with a hematologic cancer while preserving graft versus tumor immunity. In a second application, the administered hematopoietic cell transplant suppresses autoimmune disorders or disorders with an autoimmune component.

Abstract: The present disclosure provides a chimeric antigen receptor (CAR) immunotherapy for treating a hematologic cancer comprising (a) genetically modifying a population of immune effector cells comprising T cell receptors (TCRs) to stably express at least one CAR, wherein the ectodomain of the CAR specifically binds a cancer antigen; (b) expanding the population of CAR-containing immune effector cells in the presence of one or more cytokines in vitro to achieve a therapeutic dose, wherein the population of CAR-containing immune effector cells exhibits a nonexhausted memory T cell phenotype; and (c) infusing eligible subjects with the CAR-containing immune effector memory T cell phenotype population of cells as needed until the hematologic cancer in the body is destroyed. The intracellular signal transduction domain of the CAR includes 4-1BB, a CD3? T cell activation chain and a genetically engineered TLE3, which can be ectopically expressed.