Pilot trial of autologous dendritic cells loaded with tumor lysate(s) from allogeneic tumor cell lines in patients with metastatic medullary thyroid carcinoma.
Immunotherapy with autologous dendritic cells (DCs) loaded with tumor lysate(s) from allogeneic tumor cell lines is a novel strategy to induce immune responses in cancer patients. We report on a pilot trial of autologous DCs pulsed with tumor cell lysate derived from allogeneic medullary thyroid carcinoma (MTC) cell lines in patients with metastatic MTC. The purpose of this study was to assess the safety, resulting immune responses and clinical activity of the DCs. DCs were injected into a groin lymph node at 3-week intervals. Monitoring included serial calcitonin tumor marker measurements, radiological imaging and immunological in vitro tests (T-cell interferon-gamma detection assay, T-cell cytotoxicity assay). Ten patients (median age 47 years, range 29-77) were enrolled. DC vaccinations were well-tolerated and safe. After a median follow-up of 11 months, (range 7-26), 3 (30%) of 10 patients had stable disease, while 7 (70%) of the patients progressed during treatment. In 2 patients with stable disease, calcitonin decreased below treatment levels, paralleled by a T-cell-mediated immune response. Notably, treatment with DCs pulsed with a combination of different tumor cell lysates was followed by a calcitonin decrease in 4 patients who had previously experienced a calcitonin increase during monotherapy with DCs pulsed with a single lysate. Allogeneic tumor cell lysate-based DC immunotherapy is well-tolerated and safe. Combined treatment with different tumor cell lysate-pulsed DCs increases the likelihood of a calcitonin tumor marker response and should therefore be preferred over monotherapy with DCs pulsed with a single lysate.
Department of Surgery, Medical University of Vienna, A-1090 Vienna, Austria. thomas.bachleitner-hofmann@meduniwien.ac.at
Thomas
T
Bachleitner-Hofmann
Josef
J
Friedl
Michaela
M
Hassler
Hubert
H
Hayden
Peter
P
Dubsky
Monika
M
Sachet
Erwin
E
Rieder
Roswitha
R
Pfragner
Christine
C
Brostjan
Stefan
S
Riss
Bruno
B
Niederle
Michael
M
Gnant
Anton
A
Stift
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002116:Calcitonin / Q000097:blood; D019496:Cancer Vaccines; D018276:Carcinoma, Medullary / Q000175:diagnosis / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D007371:Interferon-gamma; D002116:Calcitonin