The field of cancer immunotherapy has moved forward drastically in the past 20 years, since many tumor-associated antigens (TAA) have been identified. Although various approaches for therapeutic cancer immunotherapies, including peptide-based vaccines, have been developed and clinically examined, the complexity and diversity of tumor cell characteristics and host immune cell repertoires seem to limit the therapeutic efficacy of this treatment modality. Considering the diversity of immune responses against heterogeneous tumor cells, tailored selections of vaccine antigens appropriate for individual patients could be a rational approach for developing effective cancer vaccines. We have developed a novel immunotherapeutic approach called personalized peptide vaccine (PPV), in which a maximum of four human leukocyte antigen (HLA)-matched vaccine peptides were selected based on the pre-existing host immunity before vaccination. We conducted a series of phase I and phase II clinical trials of PPV, which have shown better antigen-specific immune responses and promising clinical outcomes in patients with various types of advanced cancers. Further randomized phase III trials would be recommended to prove the clinical benefits of PPV. In addition, novel biomarkers for selecting patients who would benefit most from PPV remain to be identified.

Since both tumor cells and host immune cell repertoires are diverse and heterogeneous, immune responses against tumor-associated antigens should differ substantially among individual cancer patients. Selection of suitable peptide vaccines for individual patients based on the preexisting host immunity before vaccination could induce potent anti-tumor responses that provide clinical benefit to cancer patients. We have developed a novel immunotherapeutic approach of personalized peptide vaccination (PPV) in which a maximum of four human leukocyte antigen (HLA) class IA-matched peptides are selected for vaccination among pooled peptides on the basis of both HLA class IA type and the preexisting host immunity before vaccination. In this review, we discuss our recent results of preclinical and clinical studies of PPV for various types of advanced cancer.

Thioredoxin is a small ubiquitous protein with multiple biological functions, including cellular defense mechanisms against oxidative stress. In the present study, we investigated the role of human thioredoxin (hTRX) in the acquisition of cellular resistance to cis-diamminedichloroplatinum (

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BACKGROUND Active suppression by CD4+CD25+ regulatory T cells plays an important role in the down‐regulation of the response of T cells to foreign and self antigens. Experimental tumor models in mice revealed that regulatory T cells inhibit antitumor immune responses. The purpose of the current study was to demonstrate the possible involvement of CD4+CD25+ regulatory T cells in immune system impairment in patients with gastrointestinal malignancies. METHODS The phenotypes of lymphocytes, particularly those of CD4+CD25+ T cells, were analyzed in peripheral blood in 149 patients with gastrointestinal malignancies and in ascites in 7 patients with peritoneal dissemination. In addition, cytokine production after in vitro stimulation was examined in CD4+CD25+ and CD4+CD25− T cells isolated from patients with malignant disease. RESULTS Compared with healthy volunteers, patients with gastrointestinal malignancies had a higher proportion of CD4+CD25+ T cells in peripheral blood, due to the presence of a drastically smaller number of CD4+CD25− T cells. Among patients with gastric carcinoma, those with higher percentages of CD4+CD25+ T cells had a poorer prognosis than did those with lower percentages. CD4+CD25+ T cells also were present in greater proportions in ascites from patients who had advanced‐stage disease with peritoneal dissemination. Isolated CD4+CD25+ T cells from patients with malignant disease produced interleukin (IL)‐4 and IL‐10 but not IL‐2 or interferon‐γ; these cells also inhibited cytokine production by CD4+CD25− T cells after in vitro stimulation. CONCLUSIONS The relative increase in CD4+CD25+ regulatory T cells may be related to immunosuppression and tumor progression in patients with gastrointestinal malignancies. This finding suggests that the use of immunomodulatory therapy to treat patients with gastrointestinal malignancies may be an effective strategy. Cancer 2003;98:1089–99. © 2003 American Cancer Society. DOI 10.1002/cncr.11618