THE IMPACT OF GENE-THERAPY ON T-CELL FUNCTION IN CANCER

Studies of signal transduction by T cells are slowly identifying the i ntracellular messengers that must be generated for full T cell activat ion to take place. The recent, convincing identification of several tu mor-associated antigens (TAA) has transformed our task into trying to define the mechanisms that underlie the failure of T cells to destroy antigenic tumor cells, Although there are a variety of hypotheses that explain why tumors grow progressively, even if they are antigenic, re cent evidence suggests that T cells from tumor-bearing patients exhibi t abnormalities in signal transduction that render them unable to resp ond to appropriate activation signals, even following proper stimulati on, Gene therapy with interleukin-2 (IL-2)-secreting tumor cells in an animal model has been effective in preventing the onset of these sign aling defects, Discovery of the molecular mechanisms by which such cyt okine-secreting tumor cells induce immune responses and how they may b est be applied clinically may provide clearer indications of the direc tions to pursue to alter the balance between the T cell and the tumor cell in the patient's favor.