This edition on Tumor Immunology is focused on the preclinical development and clinical testing of adoptive cell transfer (ACT)-based immunotherapies. The rationale for ACT is strong: it involves the administration of large numbers of highly selected cells with high avidity for tumor antigens. These T cells can be programmed and activated ex vivo to exhibit antitumor effector functions. This is important because tumor-specific T cells can be inactivated at early stages of cellular transformation [1]. Furthermore, T cell infusion may be preceded by ‘conditioning’of the patient with lymphodepleting chemotherapy or total body irradiation, which enables the diminution of immunosuppressive cell types/factors followed by the infusion of tumor-specific T cells [2].

Two different strategies for the source of the adoptively transferred T cells should be distinguished: naturally-occurring T cells and genetically engineered T cells. In humans with cancer, naturally-occurring autologous tumor-specific T cells can only reliably be grown from patients with melanoma. If the desired tumor-reactive T cell repertoire is normally not present, our task is to engineer such a repertoire [3]. Although limited to the one histology of melanoma, the adoptive transfer of tumor-infiltrating lymphocytes can be highly effective. The second strategy can be more broadly applied and is conceptually similar to the clinical use of recombinant antibodies such as Herceptin and Rituxan that target non-mutated target structures on human tumors. While highly attractive, clinical experiences with genetically engineered T cells are only starting to emerge.