Viral Vectors for Immunotherapy: Vaccines and Cancer Immunotherapy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 15378

Special Issue Editor


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Guest Editor
PanTherapeutics, Rue des Remparts 4, CH-1095 Lutry, Switzerland
Interests: viral gene therapy; viral vaccines; gene expression using viral vectors; structural biology; epigenetics; nutrigenomics
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Special Issue Information

Dear Colleagues,

Immunology and immunotherapy have seen a major boost during the last few years partly due to the COVID-19 pandemic but also because of progress in cancer immunotherapy. This Special Issue on Viral Vectors of Immunotherapy aims to target both vaccine development and immunotherapy. The goal is to demonstrate the broad range of applications for various viral vectors, such as delivery vehicles for vaccine and tumor antigens, as well as their use in preclinical animal models and in clinical trials. A special emphasis is on self-replicating RNA viruses and their potential use for the delivery of recombinant viral particles, replicon RNA and layered DNA/RNA vectors.

Dr. Kenneth Lundstrom
Guest Editor

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Keywords

  • viral vectors
  • vaccines
  • immunotherapy
  • cancer therapy
  • self-replicating RNA

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Published Papers (3 papers)

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Research

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14 pages, 1413 KiB  
Article
Safety and Tolerability of the Adeno-Associated Virus Vector, AAV6.2FF, Expressing a Monoclonal Antibody in Murine and Ovine Animal Models
by Amira D. Rghei, Laura P. van Lieshout, Benjamin M. McLeod, Yanlong Pei, Jordyn A. Lopes, Nicole Zielinska, Enzo M. Baracuhy, Brenna A. Y. Stevens, Sylvia P. Thomas, Jacob G. E. Yates, Bryce M. Warner, Darwyn Kobasa, Hugues Fausther-Bovendo, Gary P. Kobinger, Khalil Karimi, Brad Thompson, Byram W. Bridle, Leonardo Susta and Sarah K. Wootton
Biomedicines 2021, 9(9), 1186; https://doi.org/10.3390/biomedicines9091186 - 9 Sep 2021
Cited by 9 | Viewed by 3985
Abstract
Adeno-associated virus (AAV) vector mediated expression of therapeutic monoclonal antibodies is an alternative strategy to traditional vaccination to generate immunity in immunosuppressed or immunosenescent individuals. In this study, we vectorized a human monoclonal antibody (31C2) directed against the spike protein of SARS-CoV-2 and [...] Read more.
Adeno-associated virus (AAV) vector mediated expression of therapeutic monoclonal antibodies is an alternative strategy to traditional vaccination to generate immunity in immunosuppressed or immunosenescent individuals. In this study, we vectorized a human monoclonal antibody (31C2) directed against the spike protein of SARS-CoV-2 and determined the safety profile of this AAV vector in mice and sheep as a large animal model. In both studies, plasma biochemical parameters and hematology were comparable to untreated controls. Except for mild myositis at the site of injection, none of the major organs revealed any signs of toxicity. AAV-mediated human IgG expression increased steadily throughout the 28-day study in sheep, resulting in peak concentrations of 21.4–46.7 µg/ mL, demonstrating practical scale up from rodent to large animal models. This alternative approach to immunity is worth further exploration after this demonstration of safety, tolerability, and scalability in a large animal model. Full article
(This article belongs to the Special Issue Viral Vectors for Immunotherapy: Vaccines and Cancer Immunotherapy)
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Review

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46 pages, 2142 KiB  
Review
Recombinant Viral Vectors for Therapeutic Programming of Tumour Microenvironment: Advantages and Limitations
by Karina Spunde, Ksenija Korotkaja and Anna Zajakina
Biomedicines 2022, 10(9), 2142; https://doi.org/10.3390/biomedicines10092142 - 31 Aug 2022
Cited by 8 | Viewed by 4225
Abstract
Viral vectors have been widely investigated as tools for cancer immunotherapy. Although many preclinical studies demonstrate significant virus-mediated tumour inhibition in synergy with immune checkpoint molecules and other drugs, the clinical success of viral vector applications in cancer therapy currently is limited. A [...] Read more.
Viral vectors have been widely investigated as tools for cancer immunotherapy. Although many preclinical studies demonstrate significant virus-mediated tumour inhibition in synergy with immune checkpoint molecules and other drugs, the clinical success of viral vector applications in cancer therapy currently is limited. A number of challenges have to be solved to translate promising vectors to clinics. One of the key elements of successful virus-based cancer immunotherapy is the understanding of the tumour immune state and the development of vectors to modify the immunosuppressive tumour microenvironment (TME). Tumour-associated immune cells, as the main component of TME, support tumour progression through multiple pathways inducing resistance to treatment and promoting cancer cell escape mechanisms. In this review, we consider DNA and RNA virus vectors delivering immunomodulatory genes (cytokines, chemokines, co-stimulatory molecules, antibodies, etc.) and discuss how these viruses break an immunosuppressive cell development and switch TME to an immune-responsive “hot” state. We highlight the advantages and limitations of virus vectors for targeted therapeutic programming of tumour immune cell populations and tumour stroma, and propose future steps to establish viral vectors as a standard, efficient, safe, and non-toxic cancer immunotherapy approach that can complement other promising treatment strategies, e.g., checkpoint inhibitors, CAR-T, and advanced chemotherapeutics. Full article
(This article belongs to the Special Issue Viral Vectors for Immunotherapy: Vaccines and Cancer Immunotherapy)
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28 pages, 1049 KiB  
Review
Molecular Mechanisms of Anti-Neoplastic and Immune Stimulatory Properties of Oncolytic Newcastle Disease Virus
by Volker Schirrmacher
Biomedicines 2022, 10(3), 562; https://doi.org/10.3390/biomedicines10030562 - 28 Feb 2022
Cited by 25 | Viewed by 6370
Abstract
Oncolytic viruses represent interesting anti-cancer agents with high tumor selectivity and immune stimulatory potential. The present review provides an update of the molecular mechanisms of the anti-neoplastic and immune stimulatory properties of the avian paramyxovirus, Newcastle Disease Virus (NDV). The anti-neoplastic activities of [...] Read more.
Oncolytic viruses represent interesting anti-cancer agents with high tumor selectivity and immune stimulatory potential. The present review provides an update of the molecular mechanisms of the anti-neoplastic and immune stimulatory properties of the avian paramyxovirus, Newcastle Disease Virus (NDV). The anti-neoplastic activities of NDV include (i) the endocytic targeting of the GTPase Rac1 in Ras-transformed human tumorigenic cells; (ii) the switch from cellular protein to viral protein synthesis and the induction of autophagy mediated by viral nucleoprotein NP; (iii) the virus replication mediated by viral RNA polymerase (large protein (L), associated with phosphoprotein (P)); (iv) the facilitation of NDV spread in tumors via the membrane budding of the virus progeny with the help of matrix protein (M) and fusion protein (F); and (v) the oncolysis via apoptosis, necroptosis, pyroptosis, or ferroptosis associated with immunogenic cell death. A special property of this oncolytic virus consists of its potential for breaking therapy resistance in human cancer cells. Eight examples of this important property are presented and explained. In healthy human cells, NDV infection activates the RIG-MAVs immune signaling pathway and establishes an anti-viral state based on a strong and uninhibited interferon α,ß response. The review also describes the molecular determinants and mechanisms of the NDV-mediated immune stimulatory effects, in which the viral hemagglutinin-neuraminidase (HN) protein plays a prominent role. The six viral proteins provide oncolytic NDV with a special profile in the treatment of cancer. Full article
(This article belongs to the Special Issue Viral Vectors for Immunotherapy: Vaccines and Cancer Immunotherapy)
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