Future Prospective of Cancer Vaccination Technology in Japan

Shimodaira, Shigetaka

doi:10.4172/2167-7689.1000143

Cited by 8 publications

(11 citation statements)

References 12 publications

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“…A preclinical study was taken as an accompanying study of the DC vaccination therapy performed in patients with cancer. The DC vaccination study (approval number PC4160014, 10 June 2016) was approved by the Kanazawa Medical University Certificated Committee for Regenerative Medicine (Class III technologies) (approval number of the Committee NB4150006) according to the Act on the Safety of Regenerative Medicine introduced in Japan on 25 November 2014 [37], and all investigations were performed according to the Declaration of Helsinki.…”

Section: New Approach To Manufacture a DC Vaccinementioning

confidence: 99%

Dendritic Cells Pre-Pulsed with Wilms’ Tumor 1 in Optimized Culture for Cancer Vaccination

et al. 2020

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With recent advances in cancer vaccination therapy targeting tumor-associated antigens (TAAs), dendritic cells (DCs) are considered to play a central role as a cell-based drug delivery system in the bioactive immune environment. Ex vivo generation of monocyte-derived DCs has been conventionally applied in adherent manufacturing systems with separate loading of TAAs before clinical use. We developed DCs pre-pulsed with Wilms’ tumor (WT1) peptides in low-adhesion culture maturation (WT1-DCs). Quality tests (viability, phenotype, and functions) of WT1-DCs were performed for process validation, and findings were compared with those for conventional DCs (cDCs). In comparative analyses, WT1-DCs showed an increase in viability and recovery of the DC/monocyte ratio, displaying lower levels of IL-10 (an immune suppressive cytokine) and a similar antigen-presenting ability in an in vitro cytotoxic T lymphocytes (CTLs) assay with cytomegalovirus, despite lower levels of CD80 and PD-L2. A clinical study revealed that WT1-specific CTLs (WT1-CTLs) were detected upon using the WT1-DCs vaccine in patients with cancer. A DC vaccine containing TAAs produced under an optimized manufacturing protocol is a potentially promising cell-based drug delivery system to induce acquired immunity.

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Section: New Approach To Manufacture a DC Vaccinementioning

confidence: 99%

Dendritic Cells Pre-Pulsed with Wilms’ Tumor 1 in Optimized Culture for Cancer Vaccination

et al. 2020

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“…The patients enrolled for DC vaccination were retrospectively evaluated to identify those who had undergone rhG-SCF treatment 24-96 h prior to apheresis to treat neutropenia. There were 90 patients with advanced cancers, including breast (17), colon/rectum (19), lung (12), ovary (11), pancreas (33), and stomach (16) cancers, who underwent a total of 108 apheresis sessions, and the number and phenotype of their DCs were evaluated. The number of monocytes was determined evaluable in 40 patients administered rhG-SCF (75 μg filgrastim; Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan) 16-18 h prior to apheresis.…”

Section: Patientsmentioning

confidence: 99%

“….2 Manufacture of a DC Vaccine and Vaccination mDCs were generated in compliance with Good Gene, Cellular, and Tissue-based Products Manufacturing Practice (GCTP) according to the Act on the Safety of Regenerative Medicine introduced in Japan on November 25,[19]. Immature DCs were generated by culturing…”

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confidence: 99%

In Vivo Administration of Granulocyte Colony-Stimulating Factor Increases the Immune Effectiveness of Dendritic Cell-Based Cancer Vaccination

Shimodaira¹,

Yanagisawa²,

Koya³

et al. 2019

Preprint

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Significant recent advances in cancer immunotherapeutics include the vaccination of cancer patients with tumor antigen-associated peptide-pulsed dendritic cells (DCs). DC vaccines with homogeneous, mature, and functional activities are required to achieve effective acquired immunity; however, the yield of autologous monocyte-derived DCs varies in each patient. Priming with a low dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16–18 h prior to apheresis resulted in 50% more harvested monocytes, with a significant increase in the ratio of CD11c+CD80+ DCs/apheresed monocytes. The detection of antigen-specific cytotoxic T lymphocytes after Wilms’ tumor 1-pulsed DC vaccination was higher in patients treated with rhG-CSF than those who were not, based on immune monitoring using tetramer analysis. Our study is the first to report that DC vaccines for cancer immunotherapy primed with low-dose rhG-CSF are expected to achieve higher acquired immunogenicity.

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“…Mature DCs (mDCs) were generated under Good Gene, Cell and Tissue Manufacturing Practice, conditions according to the "The Act on the Safety of Regenerative Medicine" introduced in Japan on November 25, 2014 (54). Mononuclear cell-rich fractions (165 ml) were isolated from 4,000 ml of the patient's blood through apheresis using a COM.TEC ® cell separator (Fresenius Kabi Japan K.K., Tokyo, Japan).…”

Section: Manufacture Of a DC Vaccinementioning

confidence: 99%

Dendritic Cell-Based Cancer Immunotherapy Targeting Wilms’ Tumor 1 for Pediatric Cancer

et al. 2016

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The treatment of advanced pediatric cancers that have metastasized to distant organs remains difficult. Investigations evaluating the potential treatment of these cancers using therapeutic vaccination with an active dendritic cell (DC)-based immunotherapy are also being conducted. This method induces an efficient immune response by the acquired immune system against tumor-associated antigens. Cancer vaccination therapies have been prepared using autologous monocyte-derived mature DCs exposed to granulocyte-macrophage colony-stimulating factor Shimodaira et al. 114 and interleukin-4, which are the molecules principally attributed to the presence of tumorassociated antigens. Wilms' tumor 1 (WT1), an attractive target antigen that has been widely detected in cancers including sarcoma and leukemia, has been shown to be the most potent tumor-associated antigen. DC-based immunotherapy targeting WT1 may have a potentially strong therapeutic activity against cancers. DC vaccines primed with human leukocyte antigen (HLA) class I-/II-restricted WT1 peptides (WT1-DC) are a feasible option. A 6-year-old girl with neuroblastoma and a 14-year-old girl with WT received autologous DC vaccination pulsed with a modified WT1 peptide compatible with HLA-A*24:02. The patients received 20 and 25 vaccines, respectively, and experienced no adverse effects aside from a grade 2 skin reaction at the injection site and a fever with tolerable elevation. WT1tetramer analysis after vaccination detected WT1-specific immune responses. This treatment strategy may be safe, tolerable, and even feasible for all patients who are refractory to treatment and for pediatric patients who have relapsed with neoplasms.

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Future Prospective of Cancer Vaccination Technology in Japan

Cited by 8 publications

References 12 publications

Dendritic Cells Pre-Pulsed with Wilms’ Tumor 1 in Optimized Culture for Cancer Vaccination

Dendritic Cells Pre-Pulsed with Wilms’ Tumor 1 in Optimized Culture for Cancer Vaccination

In Vivo Administration of Granulocyte Colony-Stimulating Factor Increases the Immune Effectiveness of Dendritic Cell-Based Cancer Vaccination

Dendritic Cell-Based Cancer Immunotherapy Targeting Wilms’ Tumor 1 for Pediatric Cancer

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