Oncolytic virus
Oncolytic viruses are viruses that kill tumor cells directly or indirectly. Oncolytic viruses have different mechanisms of action, for example, by infecting tumor cells and lyse generate an immune response or introduce toxins and tumor suppressor genes in tumor cells. They are experimentally in the context of oncolytic virotherapy (English: oncolytic virotherapy cancer ) used for the treatment of cancer.
Properties
An example of a naturally occurring oncolytic virus is the Seneca Valley virus. Most oncolytic viruses are genetically created and adapted to their host cells and possibly toxic, inhibiting angiogenesis, immunogenic, immunomodulatory or tumor suppressor transgenes.
Oncolytic viruses should be as specific as possible reproduce only in tumor cells and thereby destroy the tumor ( oncolysis ). The approach is based on the assumption that oncolytic viruses selectively infect tumors, simultaneously also induce a specific immune response and can not cause serious side effects. The goal is to achieve a systemic application in which well as tumor metastasis in the whole body can be infected.
Furthermore, it could be a therapeutic alternative for tumors that can not be surgically removed or have developed a resistance to chemotherapy or radiation therapy. Also possibly synergies through the combination of oncolytic HSV and standard treatments such as chemotherapy can be achieved.
Objectives of the genetic modification is therefore an improvement in the specificity, efficiency or long-term effects, the expression of a transgene or the avoidance of immunosuppression or an over-reaction of the immune system.
Adverse effects were severe infection profiles with increased morbidity and mortality, and an immune response against the virus in terms of a vector immunity in the first oncolytic viruses - although symptom free - led to a premature degradation of oncolytic viruses before their target cells have been achieved.
Currently, various viruses or derived viral vectors are being studied in clinical trials, including adenoviruses, herpes simplex viruses ( oHSV ), reovirus, parvovirus B19, smallpox virus, measles virus, Sendai virus, Newcastle disease virus, picornaviruses and Seneca Valley virus. In contrast to viral vectors for gene therapy or for use as vaccines, however, is a replication of oncolytic viruses in the host often desirable ( replication capacity ). Due to the replication competence, the effectiveness of oncolytic viruses is increased.
History
The relationship between a viral infection and tumor regression was described in 1904, in cervical carcinoma, Burkitt's lymphoma and Hodgkin's lymphoma. From the mid-20th century, immunization experiments were carried out against tumors. In the sixties, the first successes with poliovirus in HeLa cells bearing guinea pigs were obtained. And adenovirus, Coxsackie virus, and several others were examined. The oncolysis produced was neither complete nor lasting. Due to lack of success and lack of genetic engineering methods virotherapy were largely ceased in the following years.
Clinical phases
The world's first approved oncolytic virus is the H101 virus ( Oncorine ®) Shanghai Sunway Biotech, which was approved in China in 2005. In this virus, and the like Onyx -15 virus, viral genes have been removed, which interact with p53. Although these viruses infect not only tumor cells, but preferably kill tumor cells. During long- term survival rates of patients are unknown, the short-term response rate when treated with H101 and chemotherapy is twice as high compared to treatment with chemotherapy alone. The response rate increases when the virus is injected directly into the tumor and the resulting temperature is not suppressed.
- OncoVEX GM -CSF by Biovex been tested in phase III in patients with advanced melanoma and head and neck cancers.
- REOLYSIN Oncolytics Biotech is in Phase III against head and neck cancers
- JX- 594 of Jennerex is in Phase II against hepatocellular carcinomas. JX -594 is a thymidine kinase -deleted vaccinia virus with GM -CSF.
- NTX -010 is in Phase II Small cell lung against.
- CGTG -102 ( Ad5/3-D24-GMCSF ) of Oncos Therapeutics is in Phase I.
- GL ONC1 of Genelux is in Phase I solid tumor.
- Cavatak is in Phase II against malignant melanoma.
- Oncorine, approved in China for head and neck cancers, based on the H101 virus.