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Endocrinology Vol. 142, No. 3 1017-1023
Copyright © 2001 by The Endocrine Society


ARTICLES

Induction of a Cellular and Humoral Immune Response against Preprocalcitonin by Genetic Immunization: A Potential New Treatment for Medullary Thyroid Carcinoma1

K. Haupt, F. Siegel, M. Lu, D. Yang, G. Hilken, K. Mann, M. Roggendorf and B. Saller

Institute for Virology, Division of Endocrinology, Department of Internal Medicine (K.M., B.S.), and Central Animal Laboratory (G.H.), University of Essen, 45122 Essen, Germany

Address all correspondence and requests for reprints to: Katharina Haupt, M.D., Institute for Virology, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany.

Currently, no effective therapy exists for patients suffering from progressive medullary thyroid carcinoma (MTC), a calcitonin (CT)-secreting C cell tumor. As CT, which arises from the precursor protein preprocalcitonin (PPCT), is expressed by almost all MTC cases, these molecules may represent target antigens for immunotherapy against MTC. In our study we investigated whether DNA immunization is able to induce cellular and humoral immune responses against human PPCT (hPPCT) in mice. Antigen-encoding expression plasmids were delivered intradermally by gene gun. One group of mice received DNA encoding hPPCT only. Two groups were coinjected with mouse cytokine genes. We observed in lymphocyte proliferative assays substantial proliferation against hPPCT in mice coinjected with the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene, in contrast to mice vaccinated with hPPCT expression plasmid only. In addition, codelivery of the GM-CSF gene augmented the frequency of anti-hPPCT antibody seroconversions in sera of immunized animals, as shown by enzyme-linked immunosorbent assay. These results illustrate that cellular and humoral immune responses against hPPCT can be generated by DNA immunization and increased by coinjection of the GM-CSF gene. Our findings may have implications for the use of DNA immunization as a potential novel immunotherapeutic treatment for patients suffering from progressive MTC.




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