Disclosed herein are non-viral methods to ablate FOXP1 in T cells while effectively expressing chimeric receptors. Therefore, disclosed herein is a chimeric cell expressing a chimeric receptor, wherein the chimeric receptor is encoded by a transgene, and wherein the transgene is inserted in the genome of the cell at a location that disrupts expression or activity of an endogenous FOXP1 protein.

The present disclosure relates to low affinity chimeric antigen receptors (CARs) and CAR-T cells, which provide cytotoxicity against tumors overexpressing the proto-oncogene c-MET and alleviate on-target, off-tumor toxicities. The CAR-T cells of the present disclosure comprise low affinity anti-c-MET scFvs, which facilitate enhanced anti-tumor activity and a reduced rate of tumor relapse.

The present disclosure relates to cell therapy methods for treating solid carcinoma tumors comprising administration of immune cells expressing a chimeric antigen receptor (CAR) comprising a mutant I domain of the .sub.L subunit of human lymphocyte function-associated antigen-1 (LFA-1), which are cytotoxic against solid carcinoma tumors overexpressing ICAM-1 and alleviate on-target, off-tumor toxicities.

The present disclosure is directed to T cell receptors targeting proinsulin and isolated cell populations comprising regulatory T cells exogenously expressing the T cell receptors used to treat Type 1 Diabetes.