Induction of a cellular and humoral immune response against preprocalcitonin by genetic immunization: A potential new treatment for medullary thyroidcarcinoma

Currently, no effective therapy exists for patients suffering from progress ive medullary thyroid carcinoma (MTC), a calcitonin (CT)secreting C cell tu mor. As CT, which arises from the precursor protein preprocalcitonin (PPCT) , is expressed by almost all MTC cases, these molecules may represent targe t antigens for immunotherapy against MTC. In our study we investigated whet her DNA immunization is able to induce cellular and humoral immune response s against human PPCT (hPPCT) in mice. Antigen-encoding expression plasmids were delivered intradermally by gene gun. One group of mice received DNA en coding hPPCT only. Two groups were coinjected with mouse cytokine genes. We observed in lymphocyte proliferative assays substantial proliferation agai nst hPPCT in mice coinjected with the granulocyte-macrophage colony-stimula ting factor (GM-CSF) gene, in contrast to mice vaccinated with hPPCT expres sion plasmid only. In addition, codelivery of the GM-CSF gene augmented the frequency of anti-hPPCT antibody seroconversions in sera of immunized anim als, as shown by enzyme-linked immunosorbent assay. These results illustrat e that cellular and humoral immune responses against hPPCT can be generated by DNA immunization and increased by coinjection of the GM-CSF gene. Our f indings may have implications for the use of DNA immunization as a potentia l novel immunotherapeutic treatment for patients suffering from progressive MTC.