Abstract
Cancer is one of the leading causes of death in the world, accounting for over 30% of all deaths in Canada. Various chemotherapy and therapeutic agents are currently in practice to help combat and treat cancerous growths and to lead to cancer remission. Virotherapy is an emerging treatment that uses biotechnology to convert viruses into therapeutic agents for the treatment of specific types of cancer. This process reprograms viruses to become oncolytic and target tumor cells in the body for lysis. It also uses these viruses to recruit inflammatory and vaccination responses by the immune system to help kill surrounding tumor cells while also establishing a long immune memory to help in the case of later infections. Adenoviruses are a group of viruses that infect the membranes of the respiratory tract, eyes, intestines, urinary tract, and nervous system of humans and causing fever as well as many cold symptoms. It is also a commonly used oncolytic virus and has been demonstrated in recent studies to be a great potential tool for eliciting appropriate inflammatory responses from the immune system to kill cancer cells and inducing cell-mediated immunity to prevent against later re-infection by the specific cancer type. Advances to this virotherapy has progressed towards overcoming tumor-mediated immunosuppression, which usually allows cancerous cells to evade the immune system and escape cell destruction, especially when combined with other therapy treatments. (Goradel et al., 2019). This review will focus on the mechanism as to how engineered modified viruses stimulate the immune system for cell killing and cell-mediated immunity. There will also be an examination of several research papers with some evidence to understand the synergy being oncolytic adenovirotherapy and the immune system function to kill cancer cells. Some disadvantages and issues with using this form of therapeutic treatment will also be presented, as well as some present and future research operating to fix these issues as well as increase the overall efficacy of this cancer treatment oncolytic adenovirotherapy.
Highlights
Scope of Cancer Cancer is a group of diseases resulting from gene mutations in normal cells
This review shows the promising nature of using smart oncolytic adenoviruses to induce specific immune responses in order to kill cancer cells as well as elicit antitumor immunity that can prevent later re-infection by a specific cancer type
The papers examined in this review show the effective oncolytic nature of this virus as well as its ability to induce inflammatory and vaccination responses from the immune system
Summary
Scope of Cancer Cancer is a group of diseases resulting from gene mutations in normal cells. In tumor cells with reduced p53 function, the p53-responsive promoter will be inactive, leading to the reduced expression of the E2F antagonist This means E2F is free to bind and activate viral E2 genes in the cancerous cells resulting in viral replication and increased killing of those tumor cells (Fig. 4). Especially adenoviruses, have been demonstrated to be effective gene therapeutic vehicles for expressing immunostimulatory proteins within the tumor microenvironment to elicit antitumor immunity (Loskog, 2015, Wang, Xue, et al, 2021) This emerging therapeutic strategy has been hypothesized to be an improved method of inducing apoptosis selectively in cancer cells and of overall antitumor immunity against specific cancer types (Peter & Kuhnel, 2020). This research has demonstrated that using smart engineered adenoviruses with modulatory molecules can significantly improve the survival of a cancer patient and aid in increasing antitumor immunity
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