We have pioneered a new intracranial injection method internationally, making oncolytic virus therapy more convenient for treating brain tumor diseases. "Professor Zhang Hongwei, Vice President of Sanbo Brain Hospital at Capital Medical University, explained in detail a new achievement recently published by the team and collaborators in Nature Communications in an interview with Science and Technology Daily. This study demonstrates for the first time the safety and efficacy of a novel oncolytic virus (Ad TD nsIL12) in treating diffuse endogenous pontine gliomas (DIPG) in children. Surgical resection, chemotherapy, and radiotherapy are known as the "three axes" of tumor treatment, but traditional therapies often come with serious side effects and are difficult to completely remove tumor cells. The oncolytic virus therapy utilizes viruses to achieve precise attacks on tumor cells, inhibiting tumor growth with relatively minimal side effects. It is widely believed in the industry that oncolytic virus therapy is becoming one of the disruptive emerging tumor treatment strategies with the potential to break through clinical barriers. As the name suggests, oncolytic viruses are a type of virus that can selectively infect and destroy tumor cells, and can achieve multiple killing and are not easily resistant to drugs. ”Zhang Hongwei explained that, in terms of specific mechanisms, it is a type of immunotherapy. Because it can not only destroy tumor cells, but also guide the immune system in the body to play a role and launch an attack on tumor cells. Why do people think of using viruses to attack tumor cells? Zhang Hongwei said that oncolytic viruses were discovered by clinical doctors in their work practice. A doctor has discovered that some cancer patients' tumors unexpectedly shrink after being infected with certain viruses, and therefore speculates that the virus may be effective in treating tumors, and has begun experimental verification. Modern oncolytic virus therapy is not simply using wild viruses, but based on genetic engineering technology, carefully modifying and "arming" the virus to achieve "dual specificity". Genetic modification can enable viruses to replicate and proliferate specifically within tumor cells, without harming normal cells. This is usually achieved through the use of tumor cell specific signaling pathways, such as the absence of tumor cell specific tumor suppressor protein signaling pathways, allowing certain viruses to replicate within their cells. In addition, the transformation will also endow the virus with the ability to produce a "oncolytic" effect, which causes tumor cells to lyse and die, and releases a large amount of tumor antigens and newly generated virus particles, sounding an alarm to the body's immune system and recruiting a large number of immune cells to surround and suppress tumor cells. If the virus has not undergone these modifications, it will not only cause infection in the body, but also have poor killing effect on tumor cells and extremely low cost-benefit ratio. By optimizing and modifying viral genes to enrich their functional components, it is possible to reduce their harm to the body while retaining their ability to stimulate immune responses. ”Zhang Hongwei said. The industry believes that oncolytic virus therapy has multiple killing mechanisms and is not easily resistant to drugs. Unlike traditional targeted drugs that target a single target, oncolytic viruses attack tumor cells through a dual pathway of direct lysis and activation of the immune system. Tumor cells find it difficult to develop resistance to all mechanisms simultaneously, which reduces the risk of treatment failure. The oncolytic virus used in this published paper has been ingeniously designed to perform addition and subtraction on viral genes. It is modified based on human adenovirus type 5 (Ad5) and completed by the team of Professor Yaohe Wang, Chief Scientist of Tumor Cell and Gene Therapy at Queen Mary University of London School of Medicine in the UK. This is currently one of the most ideal oncolytic viruses. Wang Yaohe introduced that the team has found through extensive experimental research that deleting the E1A-CR2 gene fragment of the virus not only facilitates virus replication in tumor cells, improves targeting, but also reduces toxicity to normal cells; Deleting the E1B-19K gene fragment is beneficial for enhancing the virus's ability to kill tumor cells; Deleting the E3-gp19K gene fragment is beneficial in helping patients enhance the presentation of tumor specific antigens (information transmission between different cells in the immune system), thereby improving anti-tumor efficacy. The deletion of three key gene fragments can be vividly understood as removing the virus's "bandit qi", enhancing its "combat effectiveness", and activating anti-tumor "signal stations". Even more cleverly, the team not only did "subtraction" for the virus during design, but also did "addition". By introducing the non secreted interleukin-12 (IL-12) gene, when the virus enters the body, it not only maintains normal levels of IL-12 in the blood, promoting the overall immune system's anti-tumor effect, but also avoids the side effects caused by high IL-12 concentration in the blood. A large number of cell and animal experiments have fully confirmed the effectiveness of genetic modification, and the clinical trials conducted in this study further confirm the safety of oncolytic virus Ad TD nsIL12. Accelerating the clinical translation of oncolytic viruses internationally, modified oncolytic viruses are becoming a powerful tool for treating difficult and complex diseases. Last year, CG Oncology released key data from its Phase 3 clinical trial of oncolytic virus therapy, which showed that out of 110 patients treated with oncolytic virus monotherapy, 82 patients achieved complete remission, meaning their tumors completely disappeared. Clinicaltrial statistics show that there are currently over 200 oncolytic virus related clinical trials worldwide, half of which are from China, and many have advanced to the mid to late stage of clinical trials. In March of this year, the journal Nature published the results of the oncolytic virus treatment by the team led by Liang Tingbo from the First Affiliated Hospital of Zhejiang University School of Medicine in China for recurrent and refractory liver cancer. The team designed and developed a novel oncolytic virus VG161 carrying multiple immune stimulatory factors, which helped extend the median overall survival of patients from 9.4 months to 17.3 months. How to accelerate the clinical translation of oncolytic virus therapy? Zhang Hongwei believes that it is still necessary to strengthen the collaborative cooperation between basic research and clinical research, and promote the connection and transformation between the two; We can further leverage the role of academic associations, strengthen communication and cooperation between theoretical researchers and research-oriented doctors in the field of life sciences, jointly explore key paths including optimization of oncolytic virus structure design, combination therapy design, diagnosis and treatment plan optimization, etc., and provide solid evidence-based research and data support for the clinical application of oncolytic virus therapy. In the future, Zhang Hongwei's team will conduct joint treatment validation of oncolytic virus therapy with different methods such as surgery, radiotherapy, chemotherapy, antibody drug therapy, etc. based on existing diagnostic and therapeutic effects. He told reporters that malignant tumors have strong heterogeneity and require multi-target "attacks", so there is no one size fits all solution. Doctors need to integrate multiple innovative treatment methods to prolong patients' survival while ensuring their quality of life. (New Society)