“Anti-tumor vaccines have emerged as a promising therapeutic approach, whereas, their clinical responses have been limited.”

I believe that this paper was the first to demonstrate the augmentation of cellular and humoral immune responses to tumor cells and peptides in HLA-A24 positive hormone-refractory prostate cancer (HRPC) patients by peptide vaccination.

Recent advances in tumor immunology have resulted in identification of a number of antigens and their peptides recognized by tumor-reactive and human leukocyte antigen (HLA) class I-restricted cytotoxic T lymphocytes (CTLs). Anti-tumor vaccines have emerged as a promising therapeutic approach, whereas, their clinical responses have been limited. In order to develop new treatment modality for HRPC patients, we recently devised a new regime of peptide-based vaccination; the measurement of pre-existing peptide-specific CTL precursors reactive to many kinds of vaccine candidates, followed by administration of only CTL-reactive peptides (personalized peptide vaccination).

The present approach in immunotherapy for HRPC patients used a new strategy of a pre-vaccination measurement of both humoral and cellular responses to peptides, followed by administration of up to 4 peptides that had been reactive for pre-vaccination measurement among 16 vaccine candidates. Present results from a phase I study demonstrated that personalized peptide vaccination was feasible, safe, and immunologically active, and some patients had clinical responses.

Our area of interest is prostate cancer. Metastatic prostate cancer is primarily treated by hormonal therapy. However, all such treated patients eventually develop disease refractory to androgen suppression as manifested by increasing serum prostate-specific antigen (PSA) levels, progressive disease on radiographic imaging, and ultimately, symptomatic deterioration. Although the median survival duration of patients with hormone-refractory prostate cancer (HRPC) has been considerably prolonged, the improvement is unsatisfactory. Therefore, novel therapeutic agents for the treatment of HRPC are required. In order to develop new treatment modality for HRPC patients, we recently devised a new regime of peptide-based vaccination. In addition, we recently reported a benefit of the combination of this type of peptide vaccination and a low dose (280 mg/day) of estramustine phosphate in patients with metastatic HRPC who had received the prior vaccination [as published in Prostate in 2004].