Virus oncolíticos in the pipeline
Oncolytic virus therapy has recently been recognized as a promising new therapeutic approach for cancer treatment. An oncolytic virus is defined as a genetically engineered or naturally occurring virus that can selectively replicate in and kill cancer cells without harming the normal tissues. In contrast to gene therapy where a virus is used as a mere carrier for transgene delivery, oncolytic virus therapy uses the virus itself as an active drug reagent.
Historia de enfermedades víricas que encogían tumores al activar respuesta inmune
Tumor regression has often been observed during or after a naturally acquired, systemic viral infection.1, 2 In 1949, 22 patients with Hodgkin's disease were treated with sera or tissue extracts containing hepatitis virus.3 Between 1950 and 1980, many clinical trials were performed in attempts to treat cancer with wild type or naturally attenuated viruses, including hepatitis. West Nile fever, yellow fever, dengue fever and adenoviruses.4 However, these viruses were not deemed useful as therapeutics reagents because, in those days, there was no known method to control the virulence and yet retain viral replication in cancer cells
protection mechanisms against viral infection (e.g. interferon‐beta signal pathway) are impaired in the majority of cancer cells,5 that most viruses can replicate to a much greater extent in cancer cells than in normal cells
Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T‐Vec (talimogene laherparepvec), a second‐generation oncolytic herpes simplex virus type 1 (HSV‐1) armed with GM‐CSF, was recently approved as the first oncolytic virus drug in the USA and Europe. The phase III trial proved that local intralesional injections with T‐Vec in advanced malignant melanoma patients can not only suppress the growth of injected tumors but also act systemically and prolong overall survival. Other oncolytic viruses that are closing in on drug approval in North America and Europe include vaccinia virus JX‐594 (pexastimogene devacirepvec) for hepatocellular carcinoma, GM‐CSF‐expressing adenovirus CG0070 for bladder cancer, and Reolysin (pelareorep), a wild‐type variant of reovirus, for head and neck cancer. In Japan, a phase II clinical trial of G47∆, a third‐generation oncolytic HSV‐1, is ongoing in glioblastoma patients. G47∆ was recently designated as a “Sakigake” breakthrough therapy drug in Japan. This new system by the Japanese government should provide G47∆ with priority reviews and a fast‐track drug approval by the regulatory authorities. Whereas numerous oncolytic viruses have been subjected to clinical trials, the common feature that is expected to play a major role in prolonging the survival of cancer patients is an induction of specific antitumor immunity in the course of tumor‐specific viral replication. It appears that it will not be long before oncolytic virus therapy becomes a standard therapeutic option for all cancer patients.