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Vaccines
Special Issues
Clinical Effect and Immunologic Response after Dendritic Cell-Based Immunotherapy
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Clinical Effect and Immunologic Response after Dendritic Cell-Based Immunotherapy

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Cancer Vaccines and Immunotherapy".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 10608

Special Issue Editors

Prof. Dr. Shigetaka Shimodaira

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Guest Editor
Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan, Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 390-8621, Japan
Interests: dendritic cell; cancer vaccine; vaccination; acquired immunity; granulocyte colony-stimulating factor; tetramer analysis
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Shigeo Koido

E-Mail Website
Guest Editor
Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Kashiwa, Chiba 277-8567, Japan
Interests: Cancer vaccine; Dendritic cell; Immunecheck point; T cell; Wilms’ tumor 1 (WT1)
Prof. Dr. Hitoshi Kanno

E-Mail Website
Guest Editor
Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Shinjuku, Tokyo 162-8666, Japan
Interests: molecular biology; bioinformatics; genetics; pharmacogenomics; hematologic diseases

Special Issue Information

Dear Colleagues,

This Special Issue aims to focus on the progress of immune monitoring methodology and clinical investigation using dendritic cell (DC)-based cancer immunotherapy, including precision medicine. The standardized protocol for manufacturing a dendritic cell vaccine, the selection of tumor-associated antigens (TAAs), and the process for application of dendritic and related cells will also be covered in this issue.

With recent advances in cancer vaccination therapy targeting TAAs, DCs play a central role in clinical investigation and therapy. Ex vivo generation of monocyte-derived DCs has been conventionally applied in manufacturing systems with separate TAA loading. Each institute has adopted various standard operating procedures for clinical trials that comply with good manufacturing practice. Therefore, a standardized protocol is essential for the quality manufacture of DCs using either monocytes or stem cells, which, like all products certified through quality tests, must meet multicountry release criteria and regulatory guidelines.

In contrast, optimization of TAAs for various cancers is another issue critical to the efficacy of cancer immunotherapy using DCs. Several types of TAAs, for example, Wilms’ tumor 1 (WT1), are expressed in different types of solid tumors, sarcomas, and hematological malignancies; therefore, a peptide vaccination targeting this molecule has been investigated as immunotherapy for patients. Genomic medicine has advanced to the point where it can detect neoantigens in each patient, and targeting of neoantigens would be expected for future cancer treatment strategies. The development of DC-based cancer vaccines used in combination with chemotherapeutic agents, including immune checkpoint inhibitors, is also an area for further study.

A DC vaccine containing TAAs produced under an optimized manufacturing protocol is a potentially promising cell-based cancer immunotherapy to induce acquired immunity. Antigen-presenting ability in an in vitro cytotoxic T lymphocyte (CTLs) assay with TAAs is one of the main issues encountered when using DC-based vaccines in patients with cancer. Tetramer analysis and enzyme-linked immunosorbent spot (ELISpot) assays have been performed as immune monitoring for TAAs-specific CTLs; however, sensitivity and specificity remain issues to be solved. A useful approach to detect TAA-specific CTLs would be expected using genomic medicine with single-cell sequencing technology.

Prof. Dr. Shigetaka Shimodaira
Prof. Dr. Shigeo Koido
Prof. Dr. Hitoshi Kanno
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Dendritic cell
  • Tumor-associated antigen
  • Wilms’ tumor 1
  • Neoantigen
  • Cytotoxic T lymphocyte
  • Helper T lymphocyte
  • Cancer immunotherapy
  • Immune monitoring
  • Tetramer analysis
  • Enzyme-linked immunosorbent spot (ELISpot) assay
  • Clinical trial
  • Precision medicine
  • Immune checkpoint

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Published Papers (3 papers)

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13 pages, 2442 KiB  
Article
CpG-ODN Signaling via Dendritic Cells-Expressing MyD88, but Not IL-10, Inhibits Allergic Sensitization
by Ricardo Wesley Alberca, Eliane Gomes and Momtchilo Russo
Vaccines 2021, 9(7), 743; https://doi.org/10.3390/vaccines9070743 - 5 Jul 2021
Viewed by 2551
Abstract
Allergen-specific T helper (Th)2 cells orchestrate upon allergen challenge the development of allergic eosinophilic lung inflammation. Sensitization with alum adjuvant, a type 2 adjuvant, has been used extensively in animal models of allergic lung disease. In contrast, type 1 adjuvants like CpG-ODN, a [...] Read more.
Allergen-specific T helper (Th)2 cells orchestrate upon allergen challenge the development of allergic eosinophilic lung inflammation. Sensitization with alum adjuvant, a type 2 adjuvant, has been used extensively in animal models of allergic lung disease. In contrast, type 1 adjuvants like CpG-ODN, a synthetic toll-like receptor 9 agonist, inhibit the development of Th2 immunity. CpG-ODN induce type 1 and suppressive cytokines that influence Th2 cell differentiation. Here, we investigated the immune modulatory effect of CpG-ODN on allergic sensitization to OVA with alum focusing on dendritic cells (DCs) expressing the MyD88 molecule and the suppressive IL-10 cytokine. Using mice with specific cell deletion of MyD88 molecule, we showed that CpG-ODN suppressed allergic sensitization and consequent lung allergic inflammation signaling through the MyD88 pathway on dendritic cells, but not on B-cells. This inhibition was associated with an increased production of IL-10 in the bronchoalveolar lavage fluid. Sensitization to OVA with CpG-ODN of IL-10-deficient, but not wild-type mice, induced a shift towards Th1 pattern of inflammation. Employing bone marrow-derived dendritic cells (BM-DCs) pulsed with OVA for sensitizations with or without CpG-ODN, we showed that IL-10 is dispensable for the inhibition of allergic lung Th2 responses by CpG-ODN. Moreover, the lack of IL-10 on DCs was not sufficient for the CpG-ODN-induced immune-deviation towards a Th1 pattern. Accordingly, we confirmed directly the role of MyD88 pathway on DCs in the inhibition of allergic sensitization. Full article
(This article belongs to the Special Issue Clinical Effect and Immunologic Response after Dendritic Cell-Based Immunotherapy)
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19 pages, 4655 KiB  
Article
Quality Verification with a Cluster−Controlled Manufacturing System to Generate Monocyte−Derived Dendritic Cells
by Haruhiko Kawaguchi, Takuya Sakamoto, Terutsugu Koya, Misa Togi, Ippei Date, Asuka Watanabe, Kenichi Yoshida, Tomohisa Kato, Yuka Nakamura, Yasuhito Ishigaki and Shigetaka Shimodaira
Vaccines 2021, 9(5), 533; https://doi.org/10.3390/vaccines9050533 - 20 May 2021
Cited by 4 | Viewed by 3227
Abstract
Dendritic cell (DC) vaccines for cancer immunotherapy have been actively developed to improve clinical efficacy. In our previous report, monocyte−derived DCs induced by interleukin (IL)−4 with a low−adherence dish (low−adherent IL-4−DCs: la−IL-4−DCs) improved the yield and viability, as well as relatively prolonged survival [...] Read more.
Dendritic cell (DC) vaccines for cancer immunotherapy have been actively developed to improve clinical efficacy. In our previous report, monocyte−derived DCs induced by interleukin (IL)−4 with a low−adherence dish (low−adherent IL-4−DCs: la−IL-4−DCs) improved the yield and viability, as well as relatively prolonged survival in vitro, compared to IL-4−DCs developed using an adherent culture protocol. However, la−IL-4−DCs exhibit remarkable cluster formation and display heterogeneous immature phenotypes. Therefore, cluster formation in la−IL-4−DCs needs to be optimized for the clinical development of DC vaccines. In this study, we examined the effects of cluster control in the generation of mature IL-4−DCs, using cell culture vessels and measuring spheroid formation, survival, cytokine secretion, and gene expression of IL-4−DCs. Mature IL-4−DCs in cell culture vessels (cluster−controlled IL-4−DCs: cc−IL-4−DCs) displayed increased levels of CD80, CD86, and CD40 compared with that of la−IL-4−DCs. cc−IL-4−DCs induced antigen−specific cytotoxic T lymphocytes (CTLs) with a human leukocyte antigen (HLA)−restricted melanoma antigen recognized by T cells 1 (MART−1) peptide. Additionally, cc−IL-4−DCs produced higher levels of IFN−γ, possessing the CTL induction. Furthermore, DNA microarrays revealed the upregulation of BCL2A1, a pro−survival gene. According to these findings, the cc−IL-4−DCs are useful for generating homogeneous and functional IL-4−DCs that would be expected to promote long−lasting effects in DC vaccines. Full article
(This article belongs to the Special Issue Clinical Effect and Immunologic Response after Dendritic Cell-Based Immunotherapy)
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16 pages, 3306 KiB  
Article
Interferon-α-Induced Dendritic Cells Generated with Human Platelet Lysate Exhibit Elevated Antigen Presenting Ability to Cytotoxic T Lymphocytes
by Ippei Date, Terutsugu Koya, Takuya Sakamoto, Misa Togi, Haruhiko Kawaguchi, Asuka Watanabe, Tomohisa Kato, Jr. and Shigetaka Shimodaira
Vaccines 2021, 9(1), 10; https://doi.org/10.3390/vaccines9010010 - 24 Dec 2020
Cited by 13 | Viewed by 4101
Abstract
Given the recent advancements of immune checkpoint inhibitors, there is considerable interest in cancer immunotherapy provided through dendritic cell (DC)-based vaccination. Although many studies have been conducted to determine the potency of DC vaccines against cancer, the clinical outcomes are not yet optimal, [...] Read more.
Given the recent advancements of immune checkpoint inhibitors, there is considerable interest in cancer immunotherapy provided through dendritic cell (DC)-based vaccination. Although many studies have been conducted to determine the potency of DC vaccines against cancer, the clinical outcomes are not yet optimal, and further improvement is necessary. In this study, we evaluated the potential ability of human platelet lysate (HPL) to produce interferon-α-induced DCs (IFN-DCs). In the presence of HPL, IFN-DCs (HPL-IFN-DCs) displayed high viability, yield, and purity. Furthermore, HPL-IFN-DCs displayed increased CD14, CD56, and CCR7 expressions compared with IFN-DCs produced without HPL; HPL-IFN-DCs induced an extremely higher number of antigen-specific cytotoxic T lymphocytes (CTLs) than IFN-DCs, which was evaluated with a human leukocyte antigen (HLA)-restricted melanoma antigen recognized by T cells 1 (MART-1) peptide. Additionally, the endocytic and proteolytic activities of HPL-IFN-DCs were increased. Cytokine production of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α was also elevated in HPL-IFN-DCs, which may account for the enhanced CTL, endocytic, and proteolytic activities. Our findings suggest that ex-vivo-generated HPL-IFN-DCs are a novel monocyte-derived type of DC with high endocytic and proteolytic activities, thus highlighting a unique strategy for DC-based immunotherapies. Full article
(This article belongs to the Special Issue Clinical Effect and Immunologic Response after Dendritic Cell-Based Immunotherapy)
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