Medullary thyroid carcinoma: autologous tumor cell lines for dendritic cell vaccination.
BACKGROUND
Medullary thyroid carcinoma (MTC) is a calcitonin-producing tumor of the parafollicular C-cells, accounting for 5-10% of all thyroid tumors. To date, the only effective treatment is the early and total surgical removal of all neoplastic tissue. As the prognosis of patients with advanced MTC, unresectable or distant metastases is poor, and chemotherapy or irradiation is of no significant value, alternative strategies have been sought.


METHODS
A promising treatment approach for human MTC, that has already been introduced at our facility, is based on vaccination with autologous dendritic cells (DCs). Strong evidence that vaccination with autologous tumor lysate-pulsed DCs induces a specific immune response in vivo has been provided. However, the therapeutic success of this approach is sometimes critically limited by the small amount of tumor material available, especially from patients operated at an early tumor stage. Thus, it would be to the best advantage to have sufficient amounts of autologous tumor cells available for DC pulsing.


RESULTS
A method to generate viable autologous tumor cell cultures from a variety of MTC tissue samples, even when the sample size is small, has been successfully established. These cell lines maintain their neuroendocrine phenotype. In addition, it can be shown that these cells also display the biological features of neuroendocrine tumor cells at the molecular level.


CONCLUSIONS
The unlimited availability of these MTC cell lines makes it possible to specify cancerogenesis of MTC. In addition, the availability of sufficient amounts of tumor lysate from these cell lines offers the advantage of prolonged immunotherapy. Finally, these cell lines could be elegantly used as read-out system to monitor the in vivo immune response during immunotherapy with DC cell-based vaccination in patients suffering from MTC.
Pfragner
Roswitha
R
Department of Pathophysiology, Medical University of Graz, Heinrichstrasse 31, A-8010 Graz, Austria. roswitha.pfragner@meduni-graz.at
Skofitsch
Gerhard
G
Höger
Harald
H
Jech
Marion
M
Rinner
Beate
B
Siegl
Veronika
V
Niederle
Bruno
B
Gnant
Michael
M
Friedl
Josef
J
Stift
Anton
A
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D018276:Carcinoma, Medullary / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013964:Thyroid Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*
D019496:Cancer Vaccines