apoptotic cell pulsed dendritic cells elicit-t cells against mesothelioma
2004 AUG 23
Apoptotic cell-pulsed dendritic cells elicit cytotoxic T cells against mesothelioma.
"Malignant pleural mesothelioma is an uncommon tumor largely confined to the thoracic cavity, which is resistant to conventional therapies, therefore prompting an intensive search for effective treatment alternatives. This study focuses on dendritic cell (DC) vaccination for malignant pleural mesothelioma and evaluates the in vitro efficacy of antigen-loaded DC-based vaccines for the induction of major histocompatibility complex Class I-restricted antimesothelioma cytotoxic T lymphocyte responses. The source of tumor-associated antigens for HLA-A2+ DCs from healthy donors was apoptotic HLA-A2- mesothelioma cells either lacking or expressing heat shock protein 70 according to whether tumor cells were heat shocked or not before ultraviolet-mediated apoptosis," scientists in France report.
"Our results show that both apoptotic preparations were equivalent regarding the responsiveness of DCs to combined treatment with tumor necrosis factor-alpha and poly(inosinic-cytidylic) acid, as determined by similar increased expression of costimulatory molecules and interleukin-12 production," said Frederic Ebstein and colleagues at INSERM U601 in Nantes. "However, only DCs loaded with apoptotic heat shock protein 70-expressing cells were found to be potent in vitro inducers of cytotoxic T lymphocyte activity against HLA-A2+ mesothelioma cells. Such elicited cytotoxic T lymphocytes also exhibit cytotoxic activity against an HLA-A2+ melanoma cell line, suggesting recognition of shared antigens."
The researchers concluded, "These findings therefore carry the potential of offering an alternative, promising approach for the therapy of patients with malignant pleural mesothelioma."
Ebstein and his collaborators published their study in the American Journal of Respiratory and Critical Care Medicine (Cytotoxic T cell responses against mesothelioma by apoptotic cell-pulsed dendritic cells. Amer J Respir Crit Care Med, 2004;169(12):1322-1330).
Additional information can be obtained by contacting Marc Gregoire, INSERM U601, Institut de Biologie, F-44093 Nantes 01, France. E-mail: marc.gregoire@nantes.inserm.fr.
The publisher of the American Journal of Respiratory and Critical Care Medicine can be contacted at: American Thoracic Society, 1740 Broadway, New York, NY 10019-4374, USA.
The information in this article comes under the major subject areas of Mesothelioma Vaccine, Cancer Vaccine, Dendritic Cell Vaccine, Vaccine Development, Lung Cancer, Immunology, Immunotherapy, and Oncology.
