Smallpox virus against cancer
A new method for the treatment of pancreatic cancer has been created
British and Chinese scientists have developed a platform for the treatment of pancreatic cancer based on a modified smallpox virus. The results of the study are published in the Journal for ImmunoTherapy of Cancer (Marelli et al., A systematically deliverable Vaccinia virus with increased capacity for intertumoral and intratumoral spread effectively treats pancreatic cancer).
Viruses that can selectively infect and destroy cancer cells, known as oncolytic viruses, represent a promising new class of cancer therapeutics. Oncolytic viruses kill cancer cells through various mechanisms and cause strong antitumor immune responses, however, the methods of oncolytic virotherapy used are not yet able to provide a long-term cure.
To achieve the best results, it is necessary to deliver viruses directly to clusters of cancer cells, and this is not always possible, especially in the case of deeply embedded tumors or spread through the body in the form of metastases.
Researchers from the University of London Queen Mary and Zhengzhou University have developed a powerful therapeutic platform that uses a modified smallpox virus to treat pancreatic cancer, the deadliest type of cancer.
The authors modified the oncolytic smallpox vaccine virus to increase its safety. They also changed the genetic code of the virus, supplementing it with an additional copy of a protein that affects the ability of the virus to spread inside the tumor and between metastases. Also, to improve the ability of the virus to elicit an immune response against cancer, the researchers armed it with the interleukin IL-21 protein.
During preclinical trials after the introduction of a new oncolytic virus called VVL-21, scientists observed a strong antitumor immune response. The use of VVL-21 also increased the sensitivity of tumors to treatment with immunotherapy, known as immune checkpoint inhibition (ICI). To make the virus particles more resistant to the effects of the body's immune cells, the researchers injected a special substance with the virus – the inhibitor PI3Kδ.
Thus, the new therapeutic platform proposed by the authors includes a combination of a modified VVL-21 virus, a PI3Kδ inhibitor and an immune checkpoint inhibitor. The combined use of these three therapeutic agents, as shown by the results of preclinical trials, significantly increased the survival rate of patients with pancreatic cancer.
"This platform provides a powerful therapeutic tool for simultaneous exposure to several aspects of pancreatic cancer. It is convenient for administration in the form of intravenous injection and significantly improves the prospects of tumor eradication and prevention of relapses. It is also suitable for the treatment of other types of tumors," the press release says. Queen Mary University of London, the words of the head of the study, Professor Wang Yaohe (Yaohe Wang) from the Barts Cancer Institute.
The survival rate for pancreatic cancer is one of the lowest among oncological diseases. At the same time, chemotherapy and radiation therapy are relatively unsuccessful in its treatment, and promising new approaches, such as inhibition of immune control points, in the form of monotherapy do not work.
The authors hope to start clinical trials of the new platform in the near future.
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