Enhanced immunity against hepatoma induced by dendritic cells pulsed with Hsp70-H22 peptide complexes and CD40L.
OBJECTIVE
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.
Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China. g6j6@sohu.com
Jian
J
Gao
Shan Ming
SM
Luo
Ming Li
ML
Peng
Tao
T
Deng
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology* / Q000494:pharmacology; D023201:CD40 Ligand / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology* / Q000494:pharmacology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008114:Liver Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D015854:Up-Regulation
D015703:Antigens, CD; D001426:Bacterial Proteins; D019496:Cancer Vaccines; D016207:Cytokines; D006684:HLA-DR Antigens; D018840:HSP70 Heat-Shock Proteins; C444642:HSP70 protein, Mycobacterium tuberculosis; D023201:CD40 Ligand