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.
Highlights
Adenoviruses (Ads) belong to the Adenoviridae family and represent the largest known group of non-enveloped viruses
Note that MSC-mediated delivery of oncolytic AdVs (OAs) based on Adenovirus type 5 (Ad5) including ICOVIR-5 (NCT01844661) and DNX-2401 (NCT03896568) is being evaluated in clinical trials
The restoration of p53 function is a potential alternative for treating cancers, and it was found that the gain of function (GOF) of a p53 gene mutation in the transcriptional activation domain 2 (TAD2) suppressed cancer progression [72,73]
Summary
Adenoviruses (Ads) belong to the Adenoviridae family and represent the largest known group of non-enveloped viruses. Besides Ad5, many other Ad types were identified (>100) with diverse features related to their tropism, receptor usage, cellular uptake, seroprevalence in the human population, immune responses and replication efficiencies in different cell lines. For these reasons, these alternative Ad types may provide a completely new resource to design novel oncolytic agents. In the following chapters we provide a state-of-art overview to explore the complete natural diversity of human Ads as OAs. We briefly summarize molecular methods to convert alternative Ad types into OAs and we mention studies which screened other.
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