Phase II Adjuvant Cancer-specific Vaccine Therapy for Esophageal Cancer Patients Curatively Resected After Preoperative Therapy With Pathologically Positive Nodes; Possible Significance of Tumor Immune Microenvironment in its Clinical Effects.

Objectives: To elucidate the efficacy of adjuvant vaccine monotherapy using 3 Human Leukocyte Antigen (HLA)-A∗24-restricted tumor-specific peptide antigens for ESCC, upregulated lung cancer 10, cell division cycle associated 1, and KH domain-containing protein overexpressed in cancer 1.

Summary Of Background Data: ESCC patients with pathologically positive nodes (pN(+)) have a high risk for postoperative recurrence, despite curative resection after preoperative therapy. Subclinical micrometastases are an appropriate target for cancer vaccine.

Multicenter, phase II clinical trial of peptide vaccination with oral chemotherapy following curative resection for stage III colorectal cancer.

The safety and immunological responsiveness of a peptide vaccine of ring finger protein 43 and 34-kDa translocase of the outer mitochondrial membrane combined with uracil-tegafur/leucovorin (UFT/LV) was previously demonstrated in metastatic colorectal cancer (CRC) in a phase I clinical trial. To clarify the survival benefit of a peptide vaccine combined with UFT/LV as adjuvant treatment, a phase II clinical trial was conducted involving patients with stage III CRC. All enrolled patients, whose human leukocyte antigen (HLA)-A status was double-blinded, were administered the same regime of a peptide vaccine and UFT/LV chemotherapy.

Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer.

We previously reported a phase I clinical trial of a peptide vaccine ring finger protein 43 (RNF43) and 34-kDa translocase of the outer mitochondrial membrane (TOMM34) combined with uracil-tegafur (UFT)/LV for patients with metastatic colorectal cancer (CRC), and demonstrated the safety and immunological responsiveness of this combination therapy. In this study, we evaluated vaccination-induced immune responses to clarify the survival benefit of the combination therapy as adjuvant treatment. We enrolled 44 patients initially in an HLA-masked fashion.

[Survival Benefit by Combined Administration of Cyclophosphamide, Lentinula edodes Mycelia Extract(LEM), and Ganoderma lucidum Mycelia Extract(MAK)in S1018B10 Tumor-Bearing Mice].

Cyclophosphamide(CY)was intraperitoneally administered once a week to C57BL/10mice that had received Rous sarcoma virus(RSV)-induced S1018B10 syngeneic tumor transplantation and in whom tumor diameter exceeded 4.5 mm. Survival was prolonged in a group of mice that also received a mixture of LEM and MAK orally.

[Clinical trial of a seven-peptide vaccine and tegafur-uracil/leucovorin as combination therapy for advanced colorectal cancer].

We conducted a clinical trial of a seven-peptide vaccine in combination with tegafur-uracil/Leucovorin for advanced colorectal cancer. These antigenic peptides were derived from 5 proteins identified as cancer-testis antigens(ring finger protein 43 [RNF43], translocase of outer mitochondrial membrane 34[TOMM34], maternal embryonic leucine zipper kinase[MELK], forkhead box M1[FOXM1], and holliday junction recognition protein[HJURP])and 2 vascular endothelial growth factor receptors(VEGFR1 and VEGFR2). Thirty patients with advanced colorectal cancer were enrolled.

Clinical trial of a 7-peptide cocktail vaccine with oral chemotherapy for patients with metastatic colorectal cancer.

Aim: The combination of a peptide vaccine and tegafur-uracil plus leucovorin (UFT/LV) were evaluated in patients with metastatic colorectal cancer refractory to standard chemotherapy.

Patients And Methods: Thirty human leukocyte antigen (HLA)-A2402-positive patients were enrolled in the study. In a cycle of treatment, a vaccine comprising of seven synthetic peptides (five tumor antigen-derived and two vascular endothelial growth factor receptor-derived) was injected weekly, and oral chemotherapy, UFT/LV was given daily for four weeks followed by one week of rest.

[Treatment outcome of peptide vaccination for advanced colorectal cancer].

Complementary DNA( cDNA) microarray technology coupled with laser microdissection has been used to identify human leukocyte antigen (HLA)-A24-restricted epitope peptides as potential targets for cancer vaccination in colorectal cancer patients. These antigenic peptides were derived from 2 different cancer-testis antigens, ring finger protein 43 (RNF43) and translocase of outer mitochondrial membrane 34( TOMM34). We conducted a clinical trial of colorectal cancer-specific peptide( RNF43, TOMM34) vaccines with uracil/tegafur( UFT)+Leucovorin( LV) for the treatment of advanced or recurrent colorectal cancer.

[Clinical study of Peptide-cocktail vaccination with tegafur-uracil/leucovorin for advanced colorectal cancer].

cDNA microarray technology coupled with laser microdissection has been used to identify human leukocyte antigen(HLA)-A24-restricted epitope peptides as potential targets for cancer vaccination in colorectal cancer patients. These antigenic peptides were derived from 2 different testis cancer antigens, ring finger protein 43(RNF43) and translocase of outer mitochondrial membrane 34(TOMM34). We conducted a clinical trial of vaccines against colorectal cancer specific peptides(RNF43 and TOMM34) with tegafur-uracil/Leucovorin( UFT/LV) for the treatment of advanced or recurrent colorectal cancer.

[New directions in immunotherapy for malignant solid tumors].

Despite advances in treatment modalities, malignant solid tumors remain devastating maladies. Conventional treatment with chemotherapy and radiation is still only partially effective and highly toxic. In the era of increasing knowledge of the molecular biology of tumors and the interaction between the tumor and immune system, the development of targeted agents, including cancer vaccines, has emerged as a promising modality.

Phase I clinical trial of a novel peptide vaccine in combination with UFT/LV for metastatic colorectal cancer.

To test the safety and immune responses of a novel peptide vaccine derived from RNF43 (ring finger protein 43) and TOMM34 (34-kDa translocase of the outer mitochondrial membrane) administered in combination with chemotherapy in patients with metastatic colorectal cancer, a phase I clinical trial with 21 HLA-A2402-positive metastatic colorectal cancer patients was conducted. Patients received a weekly peptide vaccine (1 mg of each peptide in incomplete Freund's adjuvant) in combination with oral UFT (300 mg/m(2)/day) and UZEL (75 mg/day) for 4 weeks, followed by 1 week of rest. The protocol consisted of at least two cycles of this regimen.

[The significance of a combination of hepatic artery pump reservoir and new immunotherapy for cancer (NITC) in the treatment of colorectal liver metastasis].

Infusion of anti-cancer agents through a hepatic artery pump reservoir has been reported as a relatively useful means of treating multiple liver metastases but its mechanism of action remains to be clarified. We thought that immune responses might be involved in the mechanism of action of this therapy and attempted to test this assumption in patients with colorectal liver metastases. When the patients were divided into two groups by survival period (the 24-week or longer survival group and the less than 24-week survival group), the 24-week or longer survival group had significantly higher Th1 cytokine levels (p<0.

[Significance of gefitinib combined with immunotherapy in tumor-bearing mice].

Gefitinib (brand name: Iressa) is a drug approved for molecule-targeting therapy in lung carcinoma patients. There are still many unresolved problems concerning the safety and mechanism of action of this drug. Based on the expectation that this drug combined with immunotherapy would be highly effective, we recently conducted an experiment in tumor-bearing mice.

H-2 haplotype-dependent serum IL-12 production in tumor-bearing mice treated with various mycelial extracts.

IL-12 is considered to be one of the most important cytokines in anti-cancer therapy. We have demonstrated that substances derived from Basidiomycetes, such as active hexose-correlated compound (AHCC) and PSK induce the production of IL-12. In this study, the MHC dependency of IL-12 production induced by various mycelial extracts, PSK, AHCC and IL-X, was examined.