Science subjournal: rotavirus vaccine is expected to overcome resistance to immunocheckpoint blocking therapy

November 4, 2019 / Biogen / - -- from influenza vaccines to vaccines that help prevent varicella and measles, many vaccines are widely used to prevent infectious diseases In a new study, French researchers have raised an intriguing question: can rotavirus vaccines be reused to overcome resistance in cancer immunotherapy? They are working on resistance (or resistance) to a cancer treatment called checkpoint blocking So far, their research shows that this question can be answered with a loud "yes" The relevant research results were recently published in the Journal of Science Translational Medicine The title of the paper is "recycling rotavirus vaccines for internal immunology can over come resistance to immune checkpoint blockade" Structural diagram of rotavirus, picture from eLife, 2018, DOI: 10.7554/elife.37295.003 "We found that rotaeq and Rotarix vaccines have the characteristics of immunostimulation and tumor lysis In addition, they can directly kill cancer cells with the characteristics of immunogenic cell death In vivo, intratumoral rotavirus therapy has antitumor effect, which is mainly mediated by immunity So far, the research has been carried out in cell lines and animal models, and the results surprised experienced scientists "It's worth noting that in several mouse tumor models with immune function, intratumoral rotavirus overcomes the resistance to immunocheckpoint targeted therapy and cooperates with it," shekarian said Immunocheckpoint blockade is an innovative treatment method, which relies on drugs called immunocheckpoint inhibitors to treat a variety of cancers These drugs use the body's immune system to recognize and attack cancer cells As a checkpoint inhibitor drug, keytruda can help lead to changes in the treatment of NSCLC All checkpoint inhibitors are based on a seemingly simple principle: cancer cells have a protein called PD-L1 As a key cell in the immune system, T cells have a surface protein called PD1 PD-L1 is the ligand of PD1 which plays the role of immunocheckpoint Cunning cancer cells use their PD-L1 protein to bind to PD1 on the surface of T cells, helping them escape from T cells, allowing them to proliferate and spread Checkpoint inhibitors prevent cancer cells from escaping and hiding These drugs can be used to treat a variety of cancers, such as Hodgkins lymphoma, lung cancer, bladder cancer, ovarian cancer and kidney cancer, but the problem with them is that they sometimes don't work at all Cancer cells are resistant to checkpoint inhibitors in much the same way that superbugs are resistant to antibiotics Once drug resistance is developed, cancer cells can escape a large number of T cells, because these T cells are unable to stop the deadly cancer cells again Rotaeq and Rotarix vaccines have been approved, which have high safety and can be used as a supplement of checkpoint inhibitors Shekarian reports that the new study shows how ready-made rotavirus vaccines can be used as anti-cancer drugs as well This discovery shows that the virus, not only rotavirus, has strong anti-cancer properties Whether as a live virus vaccine or as a attenuated virus vaccine, these viral pathogens can inactivate cancer cells The oncolytic properties of common viruses can be used to enhance antitumor immune responses, the researchers wrote in the paper Shekarian and her colleagues stressed that despite the fact that many "viruses in combination with immunocheckpoint targeted therapies are currently in active clinical development The implementation of these therapies is limited by manufacturing technology bottlenecks and the risk of clinical exposure " A faster way, they say, is to test approved drugs or vaccines "Rotavirus vaccines are clinical grade products for children and adults," she said Therefore, the in situ immune strategy of intratumoral attenuated rotavirus may be implemented rapidly in clinical practice " The researchers tested several vaccines in vitro and found that the rotavirus vaccine activated NF - κ B This is a family of transcription factors that regulate important cellular activities, such as inflammation, cell growth, and apoptosis They found that rotavirus vaccines activate NF - κ B in human cell lines and block tumors that are resistant to blocking immune checkpoints In a variety of tumor models, further studies involving live or inactivated rotavirus vaccines have shown that they exhibit a sustained immune response, especially when used in combination with other immunotherapies This shows that the rotavirus vaccine which has been in production and circulation can also be used as anticancer drugs "The clinical development of this approach is the driving force behind this research using commercially available vaccines," she said She pointed out that the vaccines are safe for children and are cheap and easily accessible all over the world, including in the underdeveloped countries (bio Com) reference: 1 Tala shekarian et al Recycling rotavirus vaccines for internal immunology can overflow resistance to immune checkpoint blockade Science Translational Medicine, 2019, doi:10.1126/scitranslmed.aat5025 2.Rotavirus vaccine: A potential new role as an anticancer agent https://medicalxpress.com/news/2019-10-rotavirus-vaccine-potential-role-anticancer.html