Enhanced immunity against hepatoma induced by dendritic cells pulsed with Hsp70-H22 peptide complexes and CD40L.

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