CANCER GENE THERAPY PROGRAM

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The goal of this Program Project is to develop and test effective means for treating human cancer using gene transfer technology. The specific aim is to develop and apply strategies or introducing cytokine genes into tumor cells in order to induce a specific and effective immunologic attack on a patient's existing tumor. The components of the Program Project are: 1. Treatment of Human Melanoma and Renal Cell Carcinoma by Cytokine Gene Therapy. 2. Bladder Cancer Cytokine Gene Therapy: Human Application 3. Gene Therapy Using the Hematopoietic Stem Cell 4. Vector Design and Evaluation 5. Administration Core The initial series of clinical trials will use irradiated IL-2-producing human melanoma and renal cancer cells of HLA-A2 type injected into patients of the same HLA types with advanced disease. The potential advantages of the allogeneic approach include the pro-inflammatory effects on autologous tumor recognition. Subsequent trials will involve autologous melanoma or renal cancer cells transduced with the IL-2 gene. One trial in melanoma will involve the use of the MAGE-1 melanoma- associated antigen. In order to protect the human lymphohematopoietic system, studies will be conducted of drug resistance gene transfer into the hematopoietic stem cell and a plan is developed to construct a mouse model with a completely human lymphohematopoietic system for preclinical studies of human gene therapy. Developmental studies will also be conducted to apply cytokine gene therapy to human bladder carcinoma, an important human tumor known to respond to immunotherapy and capable of direct observation and access. New vectors and vector-cytokine gene combinations will be developed for more efficient, effective, and safe approaches to cytokine gene therapy of cancer.