Aspects of the invention described herein concern approaches to make genetically modified T cells comprising a chimeric antigen receptor for human therapy. In some alternatives the methods utilize a selection and/or isolation of CD4+ and/or CD8+ T cells from a mixed T cell population such as peripheral blood or apheresis derived mononuclear cells. Once selected/isolated the CD4+ and/or CD8+ T cells are then activated genetically modified and propagated preferably in separate or isolated cultures in the presence of one or more cytokines which support survival engraftment and/or proliferation of the cells as well as preferably promoting or inducing the retention of cell surface receptors such as CD62L CD28 and/or CD27. Included herein are also methods of treatment inhibition amelioration or elimination of a cancer by administering to a subject in need thereof one or more types of the genetically engineered T cells or compositions that comprise the genetically engineered T cell prepared as described herein.
