Many variables exist in the design of an optimized clinical protocol using autologous CAR-modified tumor-targeted T cells in the treatment of cancer. Patients undergo an initial leukapheresis to isolate autologous T cells. 1. CAR gene transfer of T cells may variably be achieved through retroviral-, lentiviral-, or transposon-mediated technology, with electroporation deemed unsuitable in this current report. 2. Optimal CAR design currently remains unclear although previously published data support a second- or third-generation CAR design over a first-generation CAR. 3. Conditioning therapy appears to favor T-cell persistence and an improved antitumor response. 4. However, the role of postinfusion exogenous cytokine support in obtaining an optimal antitumor response requires additional clinical study. Illustration by Hollie Pegram.