Heat shock fusion protein induces both specific and nonspecific anti-tumor immunity.
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 by inducing the epitope-specific CTL as well as nonspecific anti-tumor responses mediated by the HSP part of the fusion protein.
Li
Dapeng
D
Department of Molecular Biology, Jilin University, Changchun, China.
Li
Hui
H
Zhang
Peiyin
P
Wu
Xiuli
X
Wei
Hongfei
H
Wang
Li
L
Wan
Min
M
Deng
Ping
P
Zhang
Yi
Y
Wang
Junzhi
J
Liu
Yongjun
Y
Yu
Yongli
Y
Wang
Liying
L
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
D001426:Bacterial Proteins; D019496:Cancer Vaccines; D018834:Chaperonin 60; D018396:Mucin-1; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins