IL-2 gene therapy of solid tumors: An approach for the prevention of signal 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 tumor cells. A deeper understanding of the process of signal transduction following the binding of ligand by the T cell receptor can help to identify underlying defects that may be involved. Gene therapy using tumor cells genetically modified to express cytokines or surface determinants is a promising technique for stimulating antitumor responses. A potential pitfall in its application to cancer, however, is that some patients' T cells are immune suppressed and may resist stimulation by such genetically engineered vaccines. Recent studies have demonstrated that T cells from tumor-bearing patients exhibit abnormalities in signal transduction events, possibly rendering them unable to respond to activation signals. Gene therapy with interleukin 2 secreting tumor cells in an animal model has been shown effective in preventing the onset of signaling defects. A more precise definition of the molecular mechanisms that enable cytokine-secreting tumor cells to stimulate specific antitumor responses may make it feasible to optimize immunotherapeutic approaches resulting in better clinical results.