THE DEVELOPMENT OF GENE-THERAPY FOR THE TREATMENT OF CANCER

Objective The authors sought to develop new treatments for patients wi th cancer based on the genetic modification of immune lymphocytes and tumor cells designed to increase the host immune reaction against grow ing cancers. Methods Retroviral-mediated gene transduction was used to introduce genes into.tumor-infiltrating lymphocytes (TIL), and these genetically altered TIL were administered to patients with cancer. Gen es coding for cytokines were introduced into tumor cells, and these ce lls were used to immunize patients against their autologous cancers. R esults In initial studies, the gene for neomycin phosphotransferase wa s introduced into the TIL of ten patients with advanced cancer to stud y the survival and distribution of TIL in humans. These studies showed that retroviral gene transduction is a safe and practical method for adding genes to human cells and led to clinical trials in which the ge ne for tumor necrosis factor (TNF) was inserted into TIL in an effort to increase their therapeutic effectiveness. Phase I trials are curren tly underway using TIL that secrete up to 1 00 times the normal level of TNF. More recently, animal experiments have revealed that transduct ion of tumor cells with cytokine genes can enhance tumor immunogenicit y and, thus, increase the recognition of the tumor as foreign by the h ost. Clinical trials based on these observations have begun in which p atients are immunized against their own autologous tumors that were tr ansduced with the genes for TNF or interleukin-2. Conclusions Attempts at gene therapy for cancer are underway and have opened new possibili ties for the development of cancer treatments.