Effective immune responses by cytotoxic T lymphocytes and other mechanisms against experimentally induced of natural occurring cancers can provide long lasting therapeutic results fro certain tumor types. Advances in our understanding of antigen processing and presentation by MHC molecules and their recognition by the T cell receptor complex provide a molecular framework to analyze potential tumor antigens and ancillary factors which regulate the efficiency of immune effect cells for specific tumors. Evaluation of the immune response to tumors in vivo is usually limited to macroscopic evaluation of host survival, indirect measurements of tumor generating quantitative, non-invasive response are needed. This proposal will create new models of tumor and immune response imaging by retroviral introduction of the HSV1-sr39tk PET reporter gene in Moloney sarcoma virus induced hind limb rhabdomyosarcomas in C57BL/6 transgenic for the dopamine receptor (D2R) PET reporter gene expressed in sub-populations of T lymphocytes. This combination of PET reporters will allow the synchronous whole animal measurement of tumor growth and regression in concert with the spatial response should have broad applicability in the study of natural immune responses to intracellular foreign pathogens, many forms of autoimmunity, as well as alternative cancers.
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