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 by inducing the epitope‐specific CTL as well as nonspecific anti‐tumor responses mediated by the HSP part of the fusion protein.