A novel anticancer approach: SEA-anchored tumor cells expressing heat shock protein 70 onto the surface elicit strong anticancer efficacy.

Abstract

Heat shock proteins (HSP) are attractive for their initiation of anticancer specific immunity via a distinct mechanism. To facilitate the induction process, we targeted HSP onto vaccine cell surface genetically. Then, SEA (a typical superantigen) was anchored on the cells by its fusion protein with transmembrane sequence, in order to produce immune-activated microsurrounding for further improvement of specific immunity. Thereby, the dual-modified vaccine, the surface-targeting-HSP70 and SEA-anchored vaccine, was developed successfully. Both in a therapeutic setting and in a pre-immune model, the mice vaccinated with the dual-modified vaccine displayed significant lymphocyte proliferation, higher NK and CTL activity, marked tumor suppression and prolonged survival when compared with those vaccinated with the vaccine modified alone with surface-targeting HSP70 or the SEA-anchored vaccine. Of all the vaccines, the dual-modified vaccine generated the best therapeutic efficacy on melanoma-bearing mice, the strongest protection against melanoma challenge. These results suggested that the dual-modified vaccine could induce more potent anticancer specific immunity while non-specific immunity was augmented.

• Authors: Changxin Huang, Hai Yu, Qingqing Wang, Guangen Yang, Wenxue Ma, Dajing Xia, Xiaohong Chen, Pingyong Yi, Fengping Shen, Haiya Zheng, Xeutao Cao
• Journal: Immunology letters (Immunol Lett) Vol. 101 Issue 1 Pg. 71-80 (Oct 15 2005) ISSN: 0165-2478 [Print] Netherlands
• PMID: 15908014 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Enterotoxins
• HSP70 Heat-Shock Proteins
• Vaccines, Synthetic
• enterotoxin A, Staphylococcal

Topics

• Animals
• Cancer Vaccines (administration & dosage, biosynthesis, genetics, immunology)
• Cell Line, Tumor
• Cell Membrane (genetics, immunology, metabolism)
• Enterotoxins (metabolism)
• Female
• HSP70 Heat-Shock Proteins (administration & dosage, biosynthesis, genetics, immunology)
• Immunotherapy, Adoptive
• Male
• Melanoma, Experimental (genetics, immunology, metabolism, therapy)
• Mice
• Mice, Inbred C57BL
• Transfection
• Vaccines, Synthetic (administration & dosage, biosynthesis, genetics, immunology)