As a pediatric oncologist trained in hematopoietic stem-cell transplantation (HSCT), I develop and apply investigator-initiated therapies using genetically modified clinical-grade T cells. To augment anti-tumor immunity I have fashioned chimeric antigen receptors (CARs) to redirect the specificity of T cells for desired targets, such as CD19 on malignant B cells, and combined adoptive immunotherapy with immunocytokines to deliver CAR^- T cells and cytokine to tumor microenvironments. I have improved the therapeutic potential of genetically modified T cells by engineering CARs to provide a fully-competent activation signal resulting in antigen-dependent cytolysis, cytokine production, and sustained proliferation. To stimulate the recipient’s endogenous immune response, I have introduced desired recombinant antigen into T cells which then function as antigen presenting cells. Platform technologies for ex vivo manufacture and certification of genetically modified clinical-grade T cells have been developed using (i) non-viral gene transfer of DNA plasmids co-expressing CAR, conditional suicide genes for in vivo ablation, and transgenes for non-invasive imaging by positron emission tomography (PET), and (ii) artificial antigen presenting cells prepared from cell banks to numerically expand CAR⁺ T cells. These technologies are being translated into a series of gene therapy trials supported by PET to assess infused T-cell biodistribution and activation. It is expected that by combining immune-based therapies with gene engineering approaches, we will develop adjuvant technologies for effective and safe treatment of malignancies in conjunction with HSCT in children and adults alike.