Dendritic cells as potential adjuvant for immunotherapy in adrenocortical carcinoma.
OBJECTIVE
Adrenocortical carcinoma (ACC) is a rare malignancy associated with a dismal prognosis. Dendritic cells (DCs) are professional antigen-presenting cells leading to an antitumour immune response. The aim of this study was to elaborate two methods of antigen delivery to DCs and to evaluate an immunotherapy protocol in ACC patients.


METHODS
Autologous DCs were pulsed with autologous tumour lysate (TL). Fusion of DCs with tumour cells was based on a polyethylene glycol method. Two patients with metastasized hypersecretory ACC were vaccinated twice.


METHODS
In vitro data were quantified by measurement of PBMC (peripheral blood mononuclear cell) responses and cytokine secretion and by flow cytometry analyses. Clinical response was monitored by CT scan of tumour mass and measurement of angiogenic factors.


RESULTS
The maximum loading of TL was obtained at 24 h as 48.2% (+/- 26.8%) of DCs were TL-positive. The DC/tumour cell fusion efficacy was approximately 45% as shown by double positive staining for ACTH receptor and DC-specific CD83. In vivo DC vaccination resulted in positive delayed-type hypersensitivity skin reactions reflecting specific memory T-lymphocyte reaction. In vitro analyses revealed specific T-cell proliferation in patient 1 (stimulation index: 5.7 compared to pretreatment) and induction of cytotoxic granzyme B secreting T cells in patient 2 (0.41% CD8 + cells vs. 0.06% pretreatment) as indicators of specific cytotoxic T cells. Although angiogenic serum markers could be stabilized, no impact on tumour growth could be observed.


CONCLUSIONS
Our data demonstrate that autologous dendritic cells induce antigen-specific Th1 immunity in adrenocortical carcinoma. The clinical outcome, however, was not improved in the patients studied here.
Papewalis
Claudia
C
Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Duesseldorf, Germany.
Fassnacht
Martin
M
Willenberg
Holger S
HS
Domberg
Julia
J
Fenk
Roland
R
Rohr
Ulrich-Peter
UP
Schinner
Sven
S
Bornstein
Stefan R
SR
Scherbaum
Werner A
WA
Schott
Matthias
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy / Q000628:therapy*; D018268:Adrenocortical Carcinoma / Q000188:drug therapy / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000637:transplantation*; D017809:Fatal Outcome; D005434:Flow Cytometry; D006801:Humans; D006825:Hybridomas; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007267:Injections; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D008939:Mitotane / Q000627:therapeutic use; D017211:Treatment Failure
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D008939:Mitotane