The present invention provides nucleic acids vectors host cells methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor. In embodiments the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a ligand binding domain a polynucleotide comprising a customized spacer region a polynucleotide comprising a transmembrane domain and a polynucleotide comprising an intracellular signaling domain. It has been surprisingly found that the length of the spacer region can affects the ability of chimeric receptor modified T cells to recognize target cells in vitro and affects in vivo efficacy of the chimeric receptor modified T cells. Pharmaceutical formulations produced by the method and methods of using the same are also described.
