The impact of gene therapy on T cell function in cancer.
Studies of signal transduction by T cells are slowly identifying the intracellular messengers that must be generated for full T cell activation to take place. The recent, convincing identification of several tumor-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, recent evidence suggests that T cells from tumor-bearing patients exhibit abnormalities in signal transduction that render them unable to respond to appropriate activation signals, even following proper stimulation. Gene therapy with interleukin-2 (IL-2)-secreting tumor cells in an animal model has been effective in preventing the onset of these signaling defects. Discovery of the molecular mechanisms by which such cytokine-secreting tumor cells induce immune responses and how they may best be applied clinically may provide clearer indications of the directions to pursue to alter the balance between the T cell and the tumor cell in the patient's favor.
Zier
K S
KS
Division of Clinical Immunology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Gansbacher
B
B
D000818:Animals; D015316:Genetic Therapy; D006801:Humans; D007165:Immunosuppression Therapy; D016233:Immunotherapy, Active; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D007376:Interleukin-2