Oncolytic virotherapy for cancer treatment

Sima Ebrahim abadi,1,* Mona akbari,2 Rana najafi,3 Zahra sadeghzadeh,4

1. Student Research Committee, Golestan University Of Medical Sciences, Gorgan, Iran.
2. Student Research Committee, Golestan University Of Medical Sciences, Gorgan, Iran.
3. Student Research Committee, Golestan University Of Medical Sciences, Gorgan, Iran.
4. Student Research Committee, Golestan University Of Medical Sciences, Gorgan, Iran.

Abstract

Introduction

Cancer is a global concern, and a big challenge faced by researchers and physicians. over time, attention has been paid to molecular approaches for cancer treatment. these approaches are based on the molecular differences of the cancer cells and healthy ones. one of the new methods of molecular treatment for cancer is the use of viruses to kill cancer cells. the mechanism of action of these viruses is the specific detection of cancer cells and then excessive proliferation in these cells, which ultimately causes the cancer cells to burst and die. on the other hand, cell bursting results in the spread of cellular remains and tumor antigens into the tumor microenvironment, which leading to the advocation of immune system toward the cancerous cells and may overcome immunosuppression in the tumor microenvironment and promote antitumor immunity. the specific detection of cancer cells by the virus is through the specific interaction of the binding ligand at the surface of the virus with the receptor of the cancer cell surface. some viruses such as adenovirus, reovirus, measles, herpes simplex, newcastle disease virus and vaccinia have now been clinically tested as oncolytic viruses. the first approved oncolytic virus is genetically not modified echo-7 strain enterovirus rigvir, approved in latvia in 2004 which shows a promising results in melanoma treatment. the drug talimogene laherparepvec (oncovex, t-vec) was the first oncolytic herpes virus (a modified herpes simplex virus), approved by the us fda and by the ema in the eu in 2015 for the treatment of advanced melanoma. some of the viruses that are used as oncolytic virus are including: herpes simplex virus (hsv) was one of the first viruses to be used as oncolytic virus because of its appealing properties like: well-studied, easy to manipulate and relatively harmless (merely causing cold sores) so causes fewer risks. t-vec is a genetically engineered oncolytic hsv, with mutations in infectious cell proteins (icp) 34.5 and 47, while expressing us11 and granulocyte macrophage-colony stimulating factor (gm-csf). gm-csf is an immunomodulator that enhances viral oncolysis. vaccinia virus (vac): in early phase i studies, itu jx-594, a genetically engineered tk-mutant/gm-csf expressing vac, demonstrated highly promising results in patients with melanoma and hepatocellular carcinoma (hcc). adenovirus (ad): oncolytic adenoviruses are been genetically modified to take advantage of the altered tumor environment. onyx-015 is an e1b55-mutant ad that can cause oncolysis of cancer cells with mutant p53. parvovirus (pv): pv b19 can induce cell death through apoptosis in erythroid cells through non-structural proteins (ns1)-induced caspase-3 activation. parvoryx01 is a first in human, phase i/iia, dose-escalation study of h-1pv given locally and systemically in patients with recurrent glioma. reovirus (rv): reovirus preferentially targets cancer cells based on their higher rates of cell division, which differs from that of normal cells. reolysin is one of the best-studied ov and several phase i and ii studies have been completed. measles virus (mv): mv enters cells through interaction of its h protein and cellular cd46 (membrane cofactor protein) and signaling lymphocyte–activating molecule (slam). a phase i study of ip mv-cea, a carcinoembryonic antigen expressing mv, to patients with recurrent ovarian cancer has been completed.

Methods

Numerous promising ways in ovs engineering are being studied. for example, several compounds have been found that allow ovs to overcome innate antiviral immune responses. moreover, ovs that directly blunt, eliminate or evade antiviral antibody responses are under development.

Results

: clinical studies have shown promising results in using immunotherapy for cancer. however, the evasion of tumor cells from the immune system is still a big challenge.

Conclusion

Oncolytic viruses are promising immunotherapeutic agents. these viruses provide unique ways to alert the immune system, which may overcome the interactions of tumor cells with the immune system. modified viruses, in terms of tumor selectivity and potency, and optimized combinations with other immune therapies may lead to further advances in oncolytic virotherapy. with the development of viruses, as well as other immune stimulatory agents, the challenge in the field will be to successfully identify the ovs and combinations that will be the most effective for patients, particularly those with tumors that are resistant to other therapies.

Keywords

Oncolytic viral therapy, cancer, cancer treatment