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Dendritic cells as potential adjuvant for immunotherapy in adrenocortical carcinoma
- Source :
- Clinical Endocrinology. 65:215-222
- Publication Year :
- 2006
- Publisher :
- Wiley, 2006.
-
Abstract
- Summary 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. Design/patients 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. Measurements 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 ∼ 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. Conclusion 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.
- Subjects :
- Adult
Male
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Antineoplastic Agents
Cancer Vaccines
Injections
Fatal Outcome
Endocrinology
Adjuvants, Immunologic
Antigen
Antigens, Neoplasm
Internal medicine
Adrenocortical Carcinoma
medicine
Humans
Cytotoxic T cell
Hypersensitivity, Delayed
Treatment Failure
Antigen-presenting cell
Hybridomas
business.industry
Dendritic Cells
Dendritic cell
Immunotherapy
Middle Aged
Flow Cytometry
Adrenal Cortex Neoplasms
Granzyme B
Microscopy, Electron
Immunology
Cytokine secretion
Mitotane
business
CD8
Subjects
Details
- ISSN :
- 13652265 and 03000664
- Volume :
- 65
- Database :
- OpenAIRE
- Journal :
- Clinical Endocrinology
- Accession number :
- edsair.doi.dedup.....823471629feb54bb4c3f2f91b2874c69