Immunizing potential of cytokine-transduced tumor cells

The molecular definition of tumor antigens, costimulatory signals, and the possibility to genetically engineer tumor cells as well as simple protocols for efficient isolation and preparation of dendritic cells (DC) renew the interest in tumor immunotherapy and vaccination, in particular. Engineering of tumor cells with the gene of a particular cytokine is a way of releasing that cytokine at the tumor site. In contrast to bolus administration, it provides a constant supply of cytokine. If live-engineered tumor cells are injected, their proliferation results in both the provision of antigen and an increase of cytokine concentration until a physiological or a pharmacological threshold is reached, and its biological activity begins. The following inflammatory reaction is then responsible for tumor destruction, thus, turning off the initial trigger. The efficacy of this feedback action is determined by the type of cytokine, its quantity and activity, the histotype of the tumor and the molecules it releases, and its extracellular matrix (1). However, the relevant point is that a cascade of events other than tumor debulking are initiated by the transduced cytokines. Infiltration of different leukocyte types, including antigen-presenting cells (APC), and the release of secondary cytokines contribute to the induction of a systemic and memory response. Also, injection of replication in competent cells because of irradiation can exert the same effect, in this case the amount of cytokine to be released in situ to trigger the system, should be predetermined.