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Therapeutic cancer vaccines have enjoyed little success so far, although many clinical trials have been conducted. Therefore, the creation of new protocols capable of inducing an objective response is required. We examined two of these protocols in the present review. The first is a personalized protocol to take into account the immunological diversity of cytotoxic T lymphocyte responses among patients. The second is a combination therapy designed to adapt to the presence of major histocompatibility complex (MHC)-loss cancer cells. The objective response rates of our classical (non-personalized) peptide vaccines were 0%, whereas that of personalized vaccines was 11.1% in the total advanced cancers and ≥20% in malignant glioma and cervical cancers, respectively. A ≥50% decrease in serum prostate-specific antigen (PSA) was seen in 8.7% of advanced hormone refractory prostate cancer patients by personalized vaccination alone, whereas such a decrease was seen in 54% of patients when the personalized vaccination was combined with a low dose of estramustine. Based on these experiences, we propose a personalized peptide vaccine combined with chemotherapy as a new treatment modality for cancers. (Cancer Sci 2006; 97: 970–976)