The applicant has developed a powerful therapy approach against cancer which utilizes the human MHC nonrestricted cytotoxic T-cell line TALL-104. Multiple transfers of these cells into immunodeficient mice with implanted human malignancies have resulted in potent antitumor effects. In addition, remarkable anti-tumor activity attributable to the administration of the cells has been shown in spontaneous refractory tumors in dogs frequently. The applicant is currently conducting two Phase I toxicity studies in women with metastatic breast cancer and in children with refractory or recurrent tumors. The main aim of the proposed research project is to determine the tumor targeting, cell kinetics and biodistribution of the radiolabeled TALL-104 cells following intravenous administration into patients with metastatic malignancies of various organ origins. He also intends to measure the impact of this therapeutic intervention on tumor activity as measured by Fluorodeoxyglucose positron emission tomography (FDG-PET) technique. In addition he will correlate clinical and imaging findings with immunological parameters such as development of humoral and cellular immune responses against TALL-104 cells, tumor specific CTL and cytokine production and other relevant measures. He plans to enroll ten patients into this study over two years. Each patient will receive a first cycle of 5-day infusion of the TALL-104 cells followed by monthly booster administrations for up to six months duration. A percentage (10% of the total administered cells) will be labeled with [111]Indium Oxine and administered along with unlabeled cells to trace their distribution throughout the body including the tumor sites. Planar and SPECT images of the areas of interest will be acquired. FDG-PET images will be performed at baseline and the end of first cycle and at three months to determine the effects of the cells on tumor metabolism. The applicant believes the imaging techniques proposed in this application are critical for understanding the exact cell kinetics and the biodistribution of these potent cells. Also the use of the FDG-PET imaging will provide some knowledge about the efficacy of this treatment. The data generated from this study will be critical for planning effective Phase II/III trials in the future.
