This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT The outcome for patients with recurrent/metastatic osteosarcoma has not changed over the last 2 decades and most patients die of their disease. New anti-osteosarcoma therapies are need and immunotherapy holds the promise to fulfill this need. The bodys immune defense against cancers often fails because cancers either do not induce or actively inhibit immunity. We will counteract these limitations by engineering killer T cells to recognize structures on osteosarcoma cells. Using gene transfer technology, it may be possible to take advantage of the tumor killing ability of killer T cells. We propose taking the patients own T cells and putting into them a gene for an artificial structure (receptor) that will direct the T cells to the tumor and will allow it to kill it. We will put the gene for our artificial receptor into patients T cells using a modified virus (Moloney retroviral vector). These modified T-cells will then be given directly into the patients blood stream through a central line or a vein. Patients will be treated in the clinic and will be monitored closely for several hours after infusion. We will collect samples of blood from peripheral blood at regular intervals. We will look for the safety, the persistence and the function of the cells we put into the patients. Ultimately we hope to get evidence that these modified T cells are effective at fighting the cancer.