Dendritic Cells of the Future—What Is Necessary to Make DC-Based Vaccination a Clinical Success?

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Cellular/Molecular Immunology".

Deadline for manuscript submissions: closed (10 April 2021) | Viewed by 13031

Special Issue Editor


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Guest Editor
Aarhus Institute of Advanced Studies (AIAS), Department of Biomedicine, Aarhus University, Aarhus, Denmark
Interests: immunology; interface of innate and adaptive immune systems; Dendritic cells (mDC and pDC); DC interaction with CD4+ and CD8+ T cells; immunomodulation via immune checkpoints; IFNs and DCs; Human Immunodeficiency virus (HIV); replication; latency; immune evasion

Special Issue Information

Dear Colleagues,

Dendritic cells (DCs) play a pivotal role in mediating innate and adaptive immune responses. Using DCs for vaccination and therapeutic purposes has been of interest in the fields of oncology and infectious diseases for over two decades. It is safe with few adverse effects, but despite inducing favourable immune responses in preclinical studies, DC-based immunotherapy has not induced significant clinical responses. Therefore strategies to improve this promising approach remain an active topic of investigation.

This special issue in Vaccines, aims to bring together researchers from different fields of expertise (including but not limited to; cell biology, oncology and infectious diseases) and invites authors to share their ideas on how DC-based vaccination can be improved. Submission of original research and short review articles are welcome.

Dr. Renée Marije Van Der Sluis
Guest Editor

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Keywords

  • Dendritic cells
  • DCs
  • moDC
  • mDC
  • pDC
  • vaccination
  • therapeutic vaccination
  • immunomodulation
  • infectious diseases
  • oncology

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Published Papers (2 papers)

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Research

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8 pages, 474 KiB  
Communication
Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials
by Daphne W. Dumoulin, Robin Cornelissen, Koen Bezemer, Sara J. Baart and Joachim G. J. V. Aerts
Vaccines 2021, 9(5), 525; https://doi.org/10.3390/vaccines9050525 - 19 May 2021
Cited by 15 | Viewed by 5372
Abstract
Background: Malignant pleural mesothelioma (MPM) is a fatal neoplasm with, if untreated, poor survival of approximately nine months from diagnosis. Until recently, phase II–III immunotherapy trials did not show any significant benefit. The lack of immunotherapy efficacy can be explained by the fact [...] Read more.
Background: Malignant pleural mesothelioma (MPM) is a fatal neoplasm with, if untreated, poor survival of approximately nine months from diagnosis. Until recently, phase II–III immunotherapy trials did not show any significant benefit. The lack of immunotherapy efficacy can be explained by the fact that mesothelioma is a tumor with an “immune desert” phenotype, meaning a non-inflamed tumor characterized by low T-cell infiltration. By administration of DCs, which were ex-vivo cultured, exposed to (tumor-associated) antigens, and subsequently activated, this “immune desert” phenotype might be turned into an “inflamed” phenotype. Three phase I/II studies have been performed and published using activated DCs, which support this concept. We here report on the long-term survival of patients treated with DCs in three phase I/II studies. Methods: Survival data of the phase I/II trials using DC therapy in MPM patients were obtained and subsequently analyzed. In the first two trials, DCs were loaded with autologous tumor lysate. In the third trial, DCs were loaded with allogeneic mesothelioma tumor cell line lysate. Results: In the three studies combined, 29 patients with MPM were treated with DC vaccination between 2006 and 2015. At data cut-off, the median OS was 27 months (95% CI: 21–47 months). OS at 2 years was 55.2% (95% CI: 39.7–76.6%), and OS at 5 years was 20.7% (95% CI: 10.1–42.2%). Conclusions: The long-term survival of DC therapy in MPM in these three trials is promising, which is the basis for the randomized phase II/III DENIM study. This DENIM study is currently enrolling, and the results of which have to be awaited for definite conclusions. Full article
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Review

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20 pages, 1498 KiB  
Review
Dendritic Cell Tumor Vaccination via Fc Gamma Receptor Targeting: Lessons Learned from Pre-Clinical and Translational Studies
by Enrique Gómez Alcaide, Sinduya Krishnarajah and Fabian Junker
Vaccines 2021, 9(4), 409; https://doi.org/10.3390/vaccines9040409 - 20 Apr 2021
Cited by 7 | Viewed by 7040
Abstract
Despite significant recent improvements in the field of immunotherapy, cancer remains a heavy burden on patients and healthcare systems. In recent years, immunotherapies have led to remarkable strides in treating certain cancers. However, despite the success of checkpoint inhibitors and the advent of [...] Read more.
Despite significant recent improvements in the field of immunotherapy, cancer remains a heavy burden on patients and healthcare systems. In recent years, immunotherapies have led to remarkable strides in treating certain cancers. However, despite the success of checkpoint inhibitors and the advent of cellular therapies, novel strategies need to be explored to (1) improve treatment in patients where these approaches fail and (2) make such treatments widely and financially accessible. Vaccines based on tumor antigens (Ag) have emerged as an innovative strategy with the potential to address these areas. Here, we review the fundamental aspects relevant for the development of cancer vaccines and the critical role of dendritic cells (DCs) in this process. We first offer a general overview of DC biology and routes of Ag presentation eliciting effective T cell-mediated immune responses. We then present new therapeutic avenues specifically targeting Fc gamma receptors (FcγR) as a means to deliver antigen selectively to DCs and its effects on T-cell activation. We present an overview of the mechanistic aspects of FcγR-mediated DC targeting, as well as potential tumor vaccination strategies based on preclinical and translational studies. In particular, we highlight recent developments in the field of recombinant immune complex-like large molecules and their potential for DC-mediated tumor vaccination in the clinic. These findings go beyond cancer research and may be of relevance for other disease areas that could benefit from FcγR-targeted antigen delivery, such as autoimmunity and infectious diseases. Full article
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