Impact of mature dendritic cells pulsed with a novel WT1 helper peptide on the induction of HLA‑A2‑restricted WT1‑reactive CD8+ T cells

Kan, Shin; Bito, Tsuuse; Shimabuku, Masamori; Taguchi, Junichi; Ohkusa, Toshifumi; Shimodaira, Shigetaka; Sugiyama, Haruo; Koido, Shigeo

doi:10.3892/ijo.2020.5110

Cited by 3 publications

(2 citation statements)

References 30 publications

(48 reference statements)

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“…These trials commonly use dendritic cells activated by Wilms’ tumor oncogene protein-derived peptides. 17 , 18 , 19 , 20 , 21 Studies have demonstrated the safety and efficacy of vaccine therapies using Wilms' tumor oncogene protein peptides. 22 , 23 …”

Section: Introductionmentioning

confidence: 99%

Attitudes, expectations, and lived experiences of cancer patients receiving dendritic cell vaccine therapy in Japan

Kitamura,

Konya

2023

Asia-Pacific Journal of Oncology Nursing

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Section: Introductionmentioning

confidence: 99%

Attitudes, expectations, and lived experiences of cancer patients receiving dendritic cell vaccine therapy in Japan

Kitamura,

Konya

2023

Asia-Pacific Journal of Oncology Nursing

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“…The third synthetic epitope in DSP-7888 is adegramotide (WT1 34–51 : WAPVLDFAPPGASAYGSL). Within this peptide is an HLA-A*02:01-targeting sequence (VLDFAPPGA) that corresponds to amino acids 37 to 45 of the endogenous WT1 protein [ 36 ]. Thus, adegramotide can induce the activation of both cytotoxic and helper T-cell-mediated immune responses.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of action of DSP-7888 (adegramotide/nelatimotide) Emulsion, a peptide-based therapeutic cancer vaccine with the potential to turn up the heat on non-immunoreactive tumors

et al. 2022

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Background Wilms’ tumor 1 (WT1) is highly expressed in various solid tumors and hematologic malignancies. DSP-7888 (adegramotide/nelatimotide) Emulsion is an investigational therapeutic cancer vaccine comprising three synthetic epitopes derived from WT1. We evaluated the mechanism of action of DSP-7888 Emulsion, which is hypothesized to induce WT1-specific cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs). Methods The ability of nelatimotide and adegramotide to induce WT1-specific CD8+ T cells and CD4+ T cells was assessed in human peripheral blood mononuclear cells (PBMCs). The ability of DSP-7888 Emulsion to induce WT1-specific CTLs in vivo was assessed using human leukocyte antigen-I (HLA-I) transgenic mice. To assess how adegramotide, the helper peptide in DSP-7888 Emulsion, enhances WT1-specific CTLs, HLA-I transgenic mice were administered DSP-7888 or nelatimotide-only Emulsion. Interferon-gamma secretion under antigen stimulation by splenocytes co-cultured with or without tumor cells was then quantified. The effects of combination treatment with DSP-7888 Emulsion and an anti–programmed cell death protein 1 (PD-1) antibody on tumor volume and the frequency of tumor-infiltrating WT1-specific T cells were assessed in HLA-I transgenic mice implanted with WT1 antigen-positive tumors. Results The peptides in DSP-7888 Emulsion were shown to induce WT1-specific CTLs and HTLs in both human PBMCs and HLA-I transgenic mice. Unlike splenocytes from nelatimotide-only Emulsion-treated mice, splenocytes from DSP-7888 Emulsion-treated mice exhibited high levels of interferon-gamma secretion, including when co-cultured with tumor cells; interferon-gamma secretion was further enhanced by concomitant treatment with anti-PD-1. HLA-I transgenic mice administered DSP-7888 Emulsion plus anti-PD-1 experienced significantly greater reductions in tumor size than mice treated with either agent alone. This reduction in tumor volume was accompanied by increased numbers of tumor-infiltrating WT1-specific CTLs. Conclusions DSP-7888 Emulsion can promote both cytotoxic and helper T-cell-mediated immune responses against WT1-positive tumors. Adegramotide enhances CTL numbers, and the CTLs induced by treatment with both nelatimotide and adegramotide are capable of functioning within the immunosuppressive tumor microenvironment. The ability of anti-PD-1 to enhance the antitumor activity of DSP-7888 Emulsion in mice implanted with WT1-positive tumors suggests the potential for synergy.

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Peritoneal Dissemination and Malignant Ascites in Duodenal Cancer Successfully Treated With Adoptive Cell Therapy Using WT1- and MUC1-Pulsed Dendritic Cells and Activated T Cells With No Adverse Effects: A Case Report

Yagawa,

Kobayashi,

Fujita

et al. 2024

Cureus

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A satisfactory treatment for the dissemination of duodenal cancer has not yet been established. We describe a case of peritoneal dissemination and malignant ascites in duodenal cancer that was successfully treated with adoptive cell therapy with no adverse effects. A 72-year-old Japanese male patient with primary duodenal cancer with distal lymph node metastases received chemotherapy with S-1, an oral pyrimidine fluoride - derived agent, and oxaliplatin after gastrojejunal bypass, which resulted in tumor shrinkage; however, peritoneal dissemination developed. Despite the administration of a second-line chemotherapy regimen comprising irinotecan, peritoneal dissemination, malignant ascites, and cachexia continued to progress, ultimately resulting in the failure of chemotherapy. He then received adoptive cell therapy with Wilms' tumor 1 (WT1)- and mucin 1 (MUC1) peptide-pulsed dendritic cells (WT1/MUC1-DC) and CD3-activated T lymphocytes (CAT). Following the administration of this treatment eight times per week, the patient’s symptoms and malignant ascites surrounding his cancer disappeared. He developed no adverse effects from this treatment and was able to resume his usual activities without any symptoms. He has continued this treatment every few months as maintenance therapy and has been free of relapse for 54 months. This case suggests a possible beneficial effect of adoptive cell therapy with WT1/MUC1-DC and CAT for peritoneal dissemination and malignant ascites in duodenal cancer.

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Impact of mature dendritic cells pulsed with a novel WT1 helper peptide on the induction of HLA‑A2‑restricted WT1‑reactive CD8+ T cells

Cited by 3 publications

References 30 publications

Attitudes, expectations, and lived experiences of cancer patients receiving dendritic cell vaccine therapy in Japan

Attitudes, expectations, and lived experiences of cancer patients receiving dendritic cell vaccine therapy in Japan

Mechanism of action of DSP-7888 (adegramotide/nelatimotide) Emulsion, a peptide-based therapeutic cancer vaccine with the potential to turn up the heat on non-immunoreactive tumors

Peritoneal Dissemination and Malignant Ascites in Duodenal Cancer Successfully Treated With Adoptive Cell Therapy Using WT1- and MUC1-Pulsed Dendritic Cells and Activated T Cells With No Adverse Effects: A Case Report

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