Abstract | PURPOSE: Dendritic cell (DC)-based cancer vaccines have become an attractive antitumour therapeutic approach. However, clinical application of current DC-based cancer vaccines has been limited by their ineffectiveness. Heat shock protein 70 from Mycobacterium tuberculosis (TBhsp70) is known to have a potent adjuvant capability to induce maturation of DCs and thus acts as an alternative ligand to the CD40 ligand ( CD40L) on T cells to induce a T-cell response. The aim of this study is to investigate whether the combination of TBhsp70-H22 tumour- peptide complexes and CD40L might improve the antitumour efficacy for development of therapeutic DC-based vaccines against hepatoma. METHODS: The CD40, CD80, CD86 and HLA-DR expression on DCs pulsed with TBhsp70-H22 tumour- peptide complexes and soluble CD40L was studied by flow cytometric analysis, and T-helper type 1 cytokine secretion, such as IL-12p70 secretion, was tested by ELISA. The H22-specific cytotoxic T-lymphocytes (CTLs) were detected by a (51)Cr-release assay, and the in vivo antitumour immunity against hepatoma was measured by utilising H22-tumour-bearing mice after therapeutic administration. RESULTS: Up-regulation of CD40, CD80, CD86 and HLA-DR expression on DCs pulsed with TBhsp70-H22 tumour- peptide complexes and CD40L was found, which stimulated a high level of T-helper type 1 cytokine secretion, such as IL-12p70, and resulted in the induction of H22-specific CTLs. The therapeutic administration of DCs pulsed in vitro with TBhsp70-H22 tumour- peptide complexes and CD40L significantly reduced the progression of H22 tumours in mice compared with DC-Hsp70-H22 peptide complexes or DC-CD40L alone. CONCLUSIONS: Our findings demonstrate that DCs pulsed with Hsp70-H22-peptide complexes and CD40L enhance the antitumour immunity against hepatoma, which provides a novel immunotherapeutic approach against cancer.
|
Authors | Jian Gao, Shan Ming Luo, Ming Li Peng, Tao Deng |
Journal | Journal of cancer research and clinical oncology
(J Cancer Res Clin Oncol)
Vol. 138
Issue 6
Pg. 917-26
(Jun 2012)
ISSN: 1432-1335 [Electronic] Germany |
PMID | 22327301
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antigens, CD
- Bacterial Proteins
- Cancer Vaccines
- Cytokines
- HLA-DR Antigens
- HSP70 Heat-Shock Proteins
- HSP70 protein, Mycobacterium tuberculosis
- CD40 Ligand
|
Topics |
- Animals
- Antigens, CD
(biosynthesis, immunology)
- Bacterial Proteins
(immunology, pharmacology)
- CD40 Ligand
(immunology)
- Cancer Vaccines
(immunology)
- Cytokines
(immunology)
- Dendritic Cells
(drug effects, immunology)
- HLA-DR Antigens
(biosynthesis, immunology)
- HSP70 Heat-Shock Proteins
(immunology, pharmacology)
- Immunotherapy, Adoptive
(methods)
- Liver Neoplasms, Experimental
(immunology, therapy)
- Mice
- Mice, Inbred BALB C
- T-Lymphocytes, Cytotoxic
(immunology)
- T-Lymphocytes, Helper-Inducer
(immunology)
- Up-Regulation
|