A
chimeric antigen receptor (CAR) capable of targeting antigens expressed by
disease-associated cells (e.g.,
tumor cells), such as a CD19-specific CAR. A
polynucleotide encoding a CAR and optionally: i) a miRNA silencing module capable of inhibiting the expression of
immune checkpoint proteins (e.g., PD-1); ii) cytokines (e.g., membrane-bound IL-15); and / or
cell tags (e.g., HER-1 kill switches). A vector comprising the
polynucleotide. Modified
immune effector cells comprising a CAR, a
polynucleotide, or a vector. Compositions and kits comprising a CAR, a polynucleotide, a vector, and / or modified
immune effector cells. Use of CARs, polynucleotides, vectors, and / or modified
immune effector cells in the preparation of medicaments for treating diseases or conditions. A method of treating a subject suffering from a
disease or condition, comprising administering a CAR, a polynucleotide, a vector, and / or modified immune
effector cells to the subject in need.