The vaccine is polyvalence. Here we developed a vaccine with a mixture of HSP/Ps which, in addition to HSP70 or Gp96, also included HSp60 and HSP110. The antitumor effects of this mHSP/Ps vaccine were more potent than those of HSP70 or HSP60 alone and of tumor lysates used as vaccine in prophylactic immunization, Table 1. . When using this mHSP/P vaccine in mice after tumor transplantation (therapeutic immunization), the antitumor action was not effective, as we
showed in this study. The efficacy of therapeutic immunization was effective only in the combination therapy that used immunotherapeutic mHSP/Ps MK-0457 datasheet combined with CY and IL-12. Table 1 Comparison of antitumor effects of various GSK1120212 HSPs Untreated mHSP/p HSP70 HSP60 tumor lysate
No. of animals tested 10 10 10 10 10 Complete regression, no. (%) 0 4 (40%) 3 (33.3%) 1 (10%) 2 (20%) Tumor growth inhibition rate (%) 82.3 62.3 42.6 66.2 For specific immunotherapy, the identical MHC genetic molecules are important, We had no information find more about the MHC genetic molecules of S180 or MCA-207 when we selected the mouse sarcoma cell lines S180 and MCA-207 as models. However, from reported experimental information and our experiments, we knew that the S180 sarcoma cell lines can grow both in BALB/C and C57 mice, as in our control group, in which all the S180 tumors grew and were not rejected. This finding suggests S180 and BALB/C mice have the matched MHC locus even in allogenic transplantation. The MCA-207 only grew in C57 mice but was rejected in BALB/C mice, and this result suggests that the MHC of MCA-207 matched only with the MHC of C57 mice; therefore, in our animal models, the allogenic immune rejection did not occur, and the results of mHSP/P antitumor effects were not related to unmatched MHC. To identify the specificity of mHSP/P vaccine, we compared the cytolysis ratio of mHSP/Ps isolated from liver and muscle of naïve mice in vitro and
saw no cytolytic effect against S180 sarcoma. The cytolysis ratio was lower than 1%. Also, we compared the mHSP/p of S180 against rabbit liver cancer cell line vx2, and the cytolysis Florfenicol effect was lower than 10%, [data not shown]. In addition, we found that the mice vaccinated with mHSP/P of MCA207 were protected only against MCA207 but not S180 in vivo. Thus, the mHSP/P-induced immune reaction may be autologous tumor-specific, like individual vaccines. IL-12 is highly effective against established immunogenic tumors. In our study, the combination of IL-12 and Cy eradicated tumors in 30% of mice, and in IL-12-treated mice, all tumor mass necrosis and an ulcer formed before tumor eradication, suggesting the anti-angiogenesis activity of IL-12 was involved , When we combined mHSP/Ps with CY and IL-12 to enhance the immunization efficacy, the antitumor efficacy enhanced. However, with mHSP/Ps and CY alone or with mHSP/Ps and IL-12 alone, the antitumor efficacy was not improved.