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Expanding the Spectrum of Adenoviral Vectors for Cancer Therapy.

ABSTRACT: Adenoviral vectors (AdVs) have attracted much attention in the fields of vaccine development and treatment for diseases such as genetic disorders and cancer. In this review, we discuss the utility of AdVs in cancer therapies. In recent years, AdVs were modified as oncolytic AdVs (OAs) that possess the characteristics of cancer cell-specific replication and killing. Different carriers such as diverse cells and extracellular vesicles are being explored for delivering OAs into cancer sites after systemic administration. In addition, there are also various strategies to improve cancer-specific replication of OAs, mainly through modifying the early region 1 (E1) of the virus genome. It has been documented that oncolytic viruses (OVs) function through stimulating the immune system, resulting in the inhibition of cancer progression and, in combination with classical immune modulators, the anti-cancer effect of OAs can be even further enforced. To enhance the cancer treatment efficacy, OAs are also combined with other standard treatments, including surgery, chemotherapy and radiotherapy. Adenovirus type 5 (Ad5) has mainly been explored to develop vectors for cancer treatment with different modulations. Only a limited number of the more than 100 identified AdV types were converted into OAs and, therefore, the construction of an adenovirus library for the screening of potential novel OA candidates is essential. Here, we provide a state-of-the-art overview of currently performed and completed clinic trials with OAs and an adenovirus library, providing novel possibilities for developing innovative adenoviral vectors for cancer treatment.

SUBMITTER: Gao J

PROVIDER: S-EPMC7281331 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Expanding the Spectrum of Adenoviral Vectors for Cancer Therapy.

Gao Jian J Zhang Wenli W Ehrhardt Anja A

Cancers 20200502 5

Adenoviral vectors (AdVs) have attracted much attention in the fields of vaccine development and treatment for diseases such as genetic disorders and cancer. In this review, we discuss the utility of AdVs in cancer therapies. In recent years, AdVs were modified as oncolytic AdVs (OAs) that possess the characteristics of cancer cell-specific replication and killing. Different carriers such as diverse cells and extracellular vesicles are being explored for delivering OAs into cancer sites after sy ...[more]

PMID: 32370135

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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.

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Expanding the Spectrum of Adenoviral Vectors for Cancer Therapy.

Publications

Expanding the Spectrum of Adenoviral Vectors for Cancer Therapy.

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