What Is an Oncolytic Virus?

It is a type of tumor-killing virus with replication ability. The earliest report of oncolytic virus in the world was because a cervical cancer patient was found to be infected with rabies virus, and the tumor disappeared.

Oncolytic virus

In 1991, Martuza et al. Published an article in the journal Science, stating that after genetically modified HSV has a certain effect in the treatment of malignant gliomas, oncolytic virus treatment with HSV has received increasing attention. The principle is to make special oncolytic viruses by genetically modifying some of the less pathogenic viruses that exist in nature, using the inactivation or defect of tumor suppressor genes in target cells to selectively infect tumor cells. Massively replicate and eventually destroy tumor cells. At the same time, it can stimulate the immune response and attract more immune cells to continue to kill residual cancer cells. In recent decades, oncolytic virus treatment has caused widespread concern, and related research has made great progress.

Newcastle disease virus (NDV), herpes simplex virus-1 (HSV-1), reovirus, oncolytic adenovirus, etc. It is used to transform into an oncolytic virus, which specifically recognizes and infects tumor cells, eventually causing the cells to swell and destroy the tumor cells, but it cannot replicate in normal body cells without having a killing effect, and theoretically has a higher anti-tumor effect. Effect and lower side effects.

The most researched oncolytic viruses include adenovirus and herpes simplex virus (HSV). Since Martuza et al. In Science in 1991, they said that transgenic HSV has a certain effect in the treatment of malignant gliomas. In the future, oncolytic virus treatment with HSV has received increasing attention, and this treatment has now entered clinical trials.

Oncolytic viruses invade tumor cells through cell surface molecules. Therefore, one of the effective strategies for oncolytic virus treatment is to modify specific oncolytic viruses, and then use specific receptors that are overexpressed in tumor cells as Targeting, the virus invades into tumor cells and performs subsequent functions. Human epidermal growth factor receptor-2 (HER-2) is one such specific receptor, which is overexpressed in 1/4 of breast and ovarian cancer patients. With 200,000 new cases of breast and ovarian cancer every year in the United States, these patients and their families will benefit if successful oncolytic virus treatment is available.

Researchers at Ohio State University have developed a new tumor-attacking virus that not only kills tumor cells in the brain, but also blocks the growth of blood vessels in tumors. The study suggests that this oncolytic virus, which kills tumors, may be more effective in treating invasive brain tumors if it carries the protein vasculostatin, which inhibits blood vessel growth. The study was published online in Molecular Therapy.

Researchers such as Laura Menottia of the University of Bologna, Italy, conducted a study that tried to use the modified HSV for oncolytic virus treatment of HER-2 positive tumors. Researchers have used biomedical engineering methods to replace the immunoglobulin folding core in the HSV receptor-binding glycosylated protein with an anti-HER-2 single chain antibody. After HSV is modified, this recombinant can specifically enter HER-2 positive cancer cells are effective for oncolytic therapy. Due to its strong specificity, the safety data of this recombinant in mice tested by intraperitoneal injection were very good, with a half-lethal dose (LD50) greater than 5 × 108 pfu. After intratumoral injection of this recombinant into nude mice bearing human HER-2 positive cancer, the growth of cancer cells was strongly inhibited.

This study suggests that the modified HSV recombinants can be used for oncolytic virus treatment of HER-2 positive tumors with strong specificity and good safety.

Proceedings of the National Academy of Sciences 2009; 106: 9039-9044

Medical Recapitulate 2008; 14: 1482-1483

Biomedical Engineering and Clinical Medicine 2008; 12: 347-351

Clinical application of oncolytic virus