An overview of research progress on oncolytic virus in 2019 (Part Two)

1. Oncolytic adenovirus

Oncolytic adenoviruses, mostly based on human type 5 adenoviruses, are the most commonly used oncolytic viruses. It can be modified through a variety of strategies to enhance the tumor targeting of oncolytic adenoviruses, including mutating functional genes (such as E1A or E1B) in the adenovirus genome that are involved in cell cycle node regulation or (and) using tumor-specific activation. The daughter regulates the targeted transcriptional regulation of the E1A gene, and uses targeted transduction regulation of different serotype adenovirus or RGD motifs to change the way oncolytic adenovirus enters tumor cells.

In 2005, the first oncolytic adenovirus (H101, Ankerui) was approved by the CFDA for use in treating head and neck tumors. H101 oncolytic adenovirus is an E1B knockout adenovirus obtained by genetic recombination technology. It can specifically replicate and produce replication-dependent cytotoxicity in tumors lacking or abnormal p53 gene, but has no obvious cytotoxicity to normal human cells. However, compared with chemotherapy alone, the short-term response rate of H101 combined with chemotherapy has approximately doubled.

1. Oncolytic pox virus

Vaccinia virus has been used for more than 200 years as a vaccine to prevent smallpox infection, and it has detailed human safety data, so it makes it a very attractive platform for oncolytic therapy. In addition, oncolytic poxviruses can insert and express therapeutic transgenes above 50kb, and have a variety of known mechanisms of action against human and rodent tumors. Vaccinia virus is the first virus that has been shown to form a consistent and persuasive infection in tumor beds after intravenous injection.

1. Reovirus

Reovirus is an acronym for orphan virus of the respiratory tract. Reovirus usually infects the mammalian respiratory system and intestinal system. Most people have been exposed to reovirus in adulthood. However, infections usually do not cause symptoms, and the link to reovirus oncolytic capacity is found when these cells are found to replicate well and lyse in various cancer cell lines established, resolvin is a reovirus preparation that is currently being used in clinical trials to treat various cancers.

1. Polio oncolytic virus

Polio virus is a natural neuropathic agent, making it an obvious choice for selective replication of nerve cell-derived tumors. Polio virus has a positive-strand RNA genome whose translation depends on a tissue-specific internal ribosome entry site (IRES) in the 5 'untranslated region of the viral genome, which is active in neuronal-derived cells and allows translation No 5 'cap virus genome. Gromeier et al. Replaced the normal poliovirus IRES with rhinovirus IRES, altering tissue specificity. The resulting PV1 (RIPO) virus can selectively destroy malignant glioma cells while leaving normal neuronal cells unaffected.

1. M1 oncolytic virus

M1 virus is a natural virus isolated from Hainan Island by Chinese scientists. Animal experiments show that M1 virus injected through the tail vein can significantly enrich tumor tissue and inhibit tumor growth, while normal organs are not affected. Many tumor cells lack an antiviral protein, ZAP, which causes the M1 virus to infect and precisely kill these tumor cells. The normal cells have a high ZAP content, which is sufficient to resist the M1 virus without being killed.

Marketed drugs on oncolytic virus

Currently, there are only three oncolytic virus drugs approved for marketing worldwide: RIGVIR, Ankeri, and T-VEC.

1. T-VEC

In October 2015, Amgen's oncolytic virus product talimogene laherparepvec (T-VEC) based on herpes simplex virus type 1 (HSV-1) was approved by the FDA for local treatment of unresectable melanoma for the first time. In addition to deleting the ICP34.5 gene of the HSV-1 virus, T-VEC also inserted two genes encoding human GM-CSF (granulocyte-macrophage colony-stimulating factor) with a cytomegalovirus promoter to make the virus highly express GM-CSF, GM-CSF recruits DC cells to activate anti-tumor immune response. Its combination with PD1 antibody has a significant effect on the treatment of melanoma, especially metastatic melanoma!

1. H101 (Ankerui)

In October 2005, Shanghai Sanwei's recombinant human type 5 adenovirus H101 (Ankerui) was approved for marketing in China. It is mainly used for the treatment of nasopharyngeal cancer and head and neck tumors. It is the first oncolytic virus product in China. Recently, with the rise of combination medication, this product has been hot started again.

1. RIGVIR

In 2004, RIGVIR oncolytic virus product was approved for the treatment of melanoma in Latvia. This product is the world's first oncolytic virus approved for cancer treatment. The virus used by RIGVIR is wild-type Ecovirus 7 (ECHO-7). However, the clinical effectiveness of the oncolytic virus has been questioned.