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1. A method of treating cancer, comprising administering a human-derived T cell to a human subject having cancer, said human-derived T cell comprising (i) a first nucleotide sequence encoding a first short hairpin RNA (shRNA) that inhibits expression of Programmed Cell Death 1 (PD-1) and a second shRNA that inhibits expression of T cell immunoreceptor with Ig and ITIM domains (TIGIT), and (ii) a second nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular antigen recognition domain that binds a target antigen associated with the cancer, a transmembrane domain, and an intracellular signal transduction domain comprising a CD3 intracellular domain and a 4-1BB costimulatory molecule, wherein expression of the first shRNA is regulated by a first promoter and expression of the second shRNA is regulated by a second promoter, wherein the target antigen is CD19 and wherein the cancer is a CD19 positive cancer.
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