Conventional cancer treatments have been unable to eliminate malignant cells in a significant number of cancer patients despite continued improvements in the clinical protocols utilized. Adoptive immunotherapy with lymphokine-activated killer (LAK) cells and rIL-2 has provided an additional therapy that has shown evidence of effect in situations where conventional therapies have failed. Tumor-infiltrating lymphocytes (TIL's) have shown increased effectiveness in eliminating malignant cells in animals and humans when compared with LAK cells. To further increase the effectiveness of adoptive immunotherapy, Genetic Therapy, Inc., will use retrovirally mediated gene transfer to generate TIL-secreting biologically active molecules that might enhance the antitumor effect of TIL therapy. In particular, because of the central role of IL-1 in the inflammatory process, it is planned to generate TIL-secreting IL-1 by transducing TILs with a retroviral vector containing IL-1 CDNA sequences. The effect of IL-1 production by TIL's will be studied in vitro with human and mouse TIL's and in vivo with murine models to determine if there is augmentation of the efficacy of tumor killing. If significant therapeutic responses with acceptable toxicities are seen with the in vivo murine models, then applications for clinical trials for human malignancies will begin.
Anticipated Results:TIL therapy is a promising alternative therapy that has been shown to have therapeutic effects in some patients. If retrovirally mediated gene transfer into TIL cells is able to improve upon these effects, then the number of patients who will desire TIL therapy could number in the hundreds of thousands.National Cancer Institute
