A vial of virus injected into a patient will help him fight cancer. This might have sounded unbelievable 25 years ago and technologically impossible 15 years back. As the technology for creating a custom virus did not exist, all early efforts focused on finding natural oncolytic viruses. During the 1960s, promising research involved using poliovirus, adenovirus, Coxsackie virus, ECHO enterovirus RIGVIRand others. The early complications included uncontrolled viral infection, resulting in significant morbidity and mortality; the development of an immune response against the virus before it could attack the cancer cells.
Cancer Immunotherapy: Antibody Therapy
U.S. Patent Landscape Report.
Bristol-Myres Squibb and Genentech in race to drive breakthroughs in Cancer Immunotherapy.
But come circa 2015, and this is the ultimate truth. Researchers at Amgen Inc. have successfully engineered and clinically proven that viruses can be used as an immunotherapy for cancer. Viruses have been blamed through ages for causing mild to deadly diseases. Viral fevers, Ebola, AIDS, small pox and swine flu are a few to be named from the long list of diseases. The parasitic natures of these micro-organisms have been a cause for concern in various diseases. Viral infections remained untreatable through traditional antibiotics. The communication and outbreak of viral diseases like Ebola and Swine flu had been a major cause of epidemics in the recent times.
But researchers at the same time have leveraged the parasitic behaviour of viruses to engineer oncolytic viruses to kill cancer. Specially designed viruses are capable of attacking the cancerous cells and tumours while being benign to normal cells.
FDA Approves First Oncolytic Virus for Cancer Therapy
On 27 October, 2015, Amgen received an FDA approval for IMLYGIC™ (talimogene laherparepvec), a genetically modified oncolytic viral therapy indicated for the local treatment of melanoma (skin cancer). Skin cancer is the most common form of cancer in the United States. Melanoma, one type is the leading cause of skin cancer related deaths, and is most often caused by exposure to ultraviolet (UV) light. In 2012, the National Cancer Institute predicted that approximately 74,000 Americans would be diagnosed with melanoma and nearly 10,000 would die from the disease in 2015. In 2012, there were an estimated 996,587 people living with melanoma of the skin in the United States. While the latest figures are yet to be revealed, this is a troublesome situation that can find relief with oncolytic viral therapy.
IMLYGIC is a genetically modified herpes simplex virus type 1 designed to replicate within tumours and produce an immune-stimulatory protein called granulocyte-macrophage colony-stimulating factor (GM-CSF). IMLYGIC causes cell lysis, or death, which ruptures tumours, releasing tumour-derived antigens, which along with GM-CSF, may promote an anti-tumour immune response. However, the exact mechanism of action is unknown.
China ahead of U.S. to approve oncolytic virus
In 2005, regulators in China approved the world’s first oncolytic adenovirus called H101 to treat head-and-neck cancer, after evidence showed that the treatment could shrink tumours. Shanghai Sunway Biotech has received the approval and plans to expand its research effort to treat other forms of cancer.
Clinical Trials of Cancer Virotherapy
Currently there are 500 open clinical trial studies related to oncolytic viruses. The geographical distribution of clinical trial suggests that U.S. and China leads the ways.
Patenting the engineered viruses
Amgen has filed for a patent claiming talimogene laherparepvec for treating melanoma. US20150202290A1 claims “A method for the treatment of melanoma comprising administering to a patient with stages IIIb to IV melanoma an effective amount of an immune checkpoint inhibitor and a herpes simplex virus, wherein the herpes simplex virus lacks functional ICP34.5 genes, lacks a functional ICP47 gene and comprises a gene encoding human GM-CSF.’”
Virus plays 3 key roles in cancer therapy. Viruses can be vectors carrying genetic materials to kill or inhibit the growth tumours. Viruses can be oncolytic in nature, i.e. they can attack the tumour or cancer cells to expose them to immune system such that the body’s natural cytotoxic cells can recognize and kill the cancer cells.
There are currently 131 INPADOC U.S. patent families related to virotherapy for cancer. The distribution of patents in the viral vectors and oncolytic viruses categories is approximately equal.
The current oncolytic viruses are site specific i.e. the viruses are injected at the tumour site for best results. Administration of doses in remote locations is a limitation. Future oncolytic viruses would be self-driven such that when administered through blood stream can reach the remotest tumour site and attack the cancer cells.
Virus with cytotoxic particles can also be designed that can directly kill the cancer cells without requiring to stimulate the immune system, thereby reducing the risk of autoimmune and other rejection conditions.
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