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Immunology of Adenoviral Vectors in Cancer Therapy.

ABSTRACT: Adenoviruses are a commonly utilized virus for gene therapy platforms worldwide. Since adenovirus components are characterized as highly immunogenic, their immunogenicity inhibits the widespread use of adenoviral vectors to treat genetic disorders. However, stimulation of the immune response can be exploited for cancer immunotherapy platforms, and thus adenoviral vectors are used for therapeutic gene transfer, vaccines, and oncolytic agents in the cancer gene therapy field. It is now accepted that the generation of anti-tumor immune responses induced by oncolytic adenovirus treatments is critical for their anti-tumor efficacy. As such, in cancer immunotherapy with adenoviral vectors, a balance must be struck between induction of anti-adenoviral and anti-tumor immune responses. The recent trend in adenoviral-based cancer gene therapy is the development of adenoviral vectors to enhance immune responses and redirect them toward tumors. This review focuses on anti-adenoviral immunity and how adenovirotherapies skew the immune response toward an anti-tumor response.

SUBMITTER: Shaw AR

PROVIDER: S-EPMC6909129 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Immunology of Adenoviral Vectors in Cancer Therapy.

Shaw Amanda Rosewell AR Suzuki Masataka M

Molecular therapy. Methods & clinical development 20191113

Adenoviruses are a commonly utilized virus for gene therapy platforms worldwide. Since adenovirus components are characterized as highly immunogenic, their immunogenicity inhibits the widespread use of adenoviral vectors to treat genetic disorders. However, stimulation of the immune response can be exploited for cancer immunotherapy platforms, and thus adenoviral vectors are used for therapeutic gene transfer, vaccines, and oncolytic agents in the cancer gene therapy field. It is now accepted th ...[more]

PMID: 31890734

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Project description:Despite the development of novel pharmacological treatments, cardiovascular disease morbidity and mortality remain high indicating an unmet clinical need. Viral gene therapy enables targeted delivery of therapeutic transgenes and represents an attractive platform for tackling acquired and inherited cardiovascular diseases in the future. Current cardiovascular gene therapy trials in humans mainly focus on improving cardiac angiogenesis and function. Encouragingly, local delivery of therapeutic transgenes utilising first-generation human adenovirus serotype (HAd)-5 is safe in the short term and has shown some efficacy in drug refractory angina pectoris and heart failure with reduced ejection fraction. Despite this success, systemic delivery of therapeutic HAd-5 vectors targeting cardiovascular tissues and internal organs is limited by negligible gene transfer to target cells, elimination by the immune system, liver sequestration, off-target effects, and episomal degradation. To circumvent these barriers, cardiovascular gene therapy research has focused on determining the safety and efficacy of rare alternative serotypes and/or genetically engineered adenoviral capsid protein-modified vectors following local or systemic delivery. Pre-clinical studies have identified several vectors including HAd-11, HAd-35, and HAd-20-42-42 as promising platforms for local and systemic targeting of vascular endothelial and smooth muscle cells. In the past, clinical gene therapy trials were often restricted by limited scale-up capabilities of gene therapy medicinal products (GTMPs) and lack of regulatory guidance. However, significant improvement of industrial GTMP scale-up and purification, development of novel producer cell lines, and issuing of GTMP regulatory guidance by national regulatory health agencies have addressed many of these challenges, creating a more robust framework for future adenoviral-based cardiovascular gene therapy. In addition, this has enabled the mass roll out of adenovirus vector-based COVID-19 vaccines. KEY MESSAGES: First-generation HAd-5 vectors are widely used in cardiovascular gene therapy. HAd-5-based gene therapy was shown to lead to cardiac angiogenesis and improved function. Novel HAd vectors may represent promising transgene carriers for systemic delivery. Novel methods allow industrial scale-up of rare/genetically altered Ad serotypes. National regulatory health agencies have issued guidance on GMP for GTMPs.

Dataset Information

Immunology of Adenoviral Vectors in Cancer Therapy.

Publications

Immunology of Adenoviral Vectors in Cancer Therapy.

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