Heat shock fusion protein induces both specific and nonspecific anti-tumor immunity

European Journal of Immunology
Dapeng LiLiying Wang

Abstract

Mucin 1 (MUC1) is a tumor antigen, and the most important epitopes that can induce cytotoxic T lymphocytes (CTL) reside in the variable-number tandem repeats (VNTR). Heat shock protein (HSP) complexes isolated from tumors have been shown to induce specific anti-tumor immunity. HSP alone can also induce nonspecific immunity. To explore the possibility to utilize the specific anti-tumor immunity induced by MUC1 VNTR and the nonspecific immunity induced by HSP, we constructed a recombinant protein (HSP65-MUC1) by fusing Bacillus Calmette-Guérin-derived HSP65 with the MUC1 VNTR peptide and tested its ability to induce anti-tumor activities in a tumor challenge model. The growth of MUC1-expressing tumors was significantly inhibited in mice immunized with HSP65-MUC1, both before and after tumor challenge. A much larger percentage of immunized mice survived the tumor challenge than non-immunized mice. Correlating with the anti-tumor activity, HSP65-MUC1 was shown to induce MUC1-specific CTL as well as nonspecific anti-tumor immunity. In the human system, HSP65-MUC1-loaded human DC induced the generation of autologous MUC1-specific CTL in vitro. These results suggest that exogenously applied HSP65-MUC1 may be used to treat MUC1 tumors ...Continue Reading

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Citations

Jan 21, 2010·Cancer Immunology, Immunotherapy : CII·Bohan DongLiying Wang
May 1, 2012·Frontiers of Medicine·Kai Gao, Junzhi Wang
Jul 31, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jie YangRongyue Cao
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Jun 30, 2007·Regulatory Toxicology and Pharmacology : RTP·Yan HuoJunzhi Wang
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