Dendritic cell vaccination in medullary thyroid carcinoma.
OBJECTIVE
Prognosis and treatment effectiveness for medullary thyroid carcinoma (MTC) are strictly related to tumor stage. Palliative treatment options show no significant benefit. A promising treatment approach for human cancer is based on the vaccination of autologous dendritic cells (DCs).


METHODS
The objective of this study was to evaluate the effectiveness of DC vaccines in MTC patients. Therefore, we generated autologous tumor lysate-pulsed DCs from 10 patients suffering from advanced MTC for repeated vaccination. Mature DCs were derived from peripheral blood monocytes by using CD14 magnetic bead selection and subsequent culture in the presence of granulocyte macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor alpha with or without addition of IFN-gamma. DCs were loaded with tumor lysate and further injected into a groin lymph node. Toxicity, tumor marker profile, immune response, and clinical response were determined.


RESULTS
Vaccination was well tolerated and induced a positive immunological response in all of the tested patients as evaluated by in vivo delayed-type hypersensitivity reactivity or in vitro intracytoplasmic IFN-gamma detection assay. Three patients had a partial response, 1 patient presented a minor response, and 2 patients showed stable disease. The remaining 4 patients had progressive disease.


CONCLUSIONS
These data provide strong evidence that vaccination with tumor-lysate pulsed DCs results in the induction of a specific immune response in patients suffering from MTC. Objective clinical responses could be observed even for far-advanced disease. Therefore, we suggest that MTC is particularly suited for DC-based immunotherapy.
Stift
Anton
A
Department of Surgery, University of Vienna, Medical School, Vienna, Austria. A.Stift@akh-wien.ac.at
Sachet
Monika
M
Yagubian
Rubina
R
Bittermann
Clemens
C
Dubsky
Peter
P
Brostjan
Christine
C
Pfragner
Roswitha
R
Niederle
Bruno
B
Jakesz
Raimund
R
Gnant
Michael
M
Friedl
Josef
J
D000328:Adult; D000368:Aged; D002116:Calcitonin / Q000097:blood; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000097:blood; D018276:Carcinoma, Medullary / Q000097:blood / Q000473:pathology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D002116:Calcitonin