IL-2 GENE-THERAPY OF SOLID TUMORS - AN APPROACH FOR THE PREVENTION OFSIGNAL-TRANSDUCTION DEFECTS IN T-CELLS

The identification of tumor-associated antigens has focused attention on the mechanisms that underlie the failure of T cells to destroy tumo r cells. A deeper understanding of the process of signal transduction following the binding of ligand by the T cell receptor can help to ide ntify underlying defects that may be involved. Gene therapy using tumo r cells genetically modified to express cytokines or surface determina nts is a promising technique for stimulating antitumor responses. A po tential pitfall in its application to cancer, however, is that some pa tients' T cells are immune suppressed and may resist stimulation by su ch genetically engineered vaccines. Recent studies have demonstrated t hat T cells from tumor-bearing patients exhibit abnormalities in signa l transduction events, possibly rendering them unable to respond to ac tivation signals. Gene therapy with interleukin 2 secreting tumor cell s in an animal model has been shown effective in preventing the onset of signaling defects. A more precise definition of the molecular mecha nisms that enable cytokine-secreting tumor cells to stimulate specific antitumor responses may make it feasible to optimize immunotherapeuti c approaches resulting in better clinical results.