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Margret Wuttke, Claudia Papewalis, Yvonne Meyer, Caroline Kessler, Benedikt Jacobs, Holger S. Willenberg, Sven Schinner, Christine Kouatchoua, Thomas Baehring, Werner A. Scherbaum, Matthias Schott, Amino Acid-Modified Calcitonin Immunization Induces Tumor Epitope-Specific Immunity in a Transgenic Mouse Model for Medullary Thyroid Carcinoma, Endocrinology, Volume 149, Issue 11, 1 November 2008, Pages 5627–5634, https://doi.org/10.1210/en.2008-0631
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Up to now, no relevant tumor antigen has been identified in medullary thyroid carcinoma (MTC). The aim of the present study was to prove the concept of an immunization with an amino acid-modified calcitonin (CT) for the treatment of MTC in a transgenic mouse model. Amino acid-modified (human) CT has been chosen for vaccination because of its higher binding affinity to the murine H2-Kb-MHC molecule. Mice were immunized over 6 months with monthly injections of amino acid-modified CT-pulsed dendritic cells. For enumeration of tumor epitope-specific CD8+ cytotoxic T cells, tetramer analyses were performed. CT peptide-treated mice revealed a mean 0.73 ± 0.45 and 0.91 ± 0.59% positive cells, depending on the two tetramers tested, whereas no increase was seen in control protein-immunized mice (0.08–0.12% tetramer-positive cells). Importantly, the subset of CT-specific CD8+ T cells also showed a high expression of interferon-γ. In line with these results, CT-immunized mice also showed an intratumor infiltration with CD8+ T lymphocytes. Importantly, we also found a diminished tumor outgrowth of −57% and a decrease of the serum CT levels (2.0 ± 0.1 pg/ml) compared with control protein-immunized Ret/Cal mice (3.0 ± 0.4 pg/ml). In summary, we show that amino acid-modified CT is recognized from the immune system leading to a specific antitumor immune response and a diminished tumor outgrowth in transgenic MTC mice. The results are of potential importance because they might be applicable to patients with metastatic spread of a MTC.
