Abstract:Cancerisamajorpublichealthproblemintheworld.Inrecentyears,duetodiet,environment,agingpopulationandotherfactors,theglobalcancerincidenceratehasbeenincreasing,andcancerasthemaincauseofdeathhasbecomeincr
Cancer is a major public health problem in the world. In recent years, due to diet, environment, aging population and other factors, the global cancer incidence rate has been increasing, and cancer as the main cause of death has become increasingly prominent.
According to the latest global cancer data in 2020 released by the international agency for research on cancer (IARC), China has become a real cancer country. As a country with a large population in the world, China's cancer data is not optimistic. China ranks first in the world in terms of the number of new cases and deaths.
Recently, Professor nieguangjun and Professor Zhaoxiao of the national nanoscience center of the Chinese Academy of Sciences published a research paper entitled "anti bearing outer membrane vesicles as tumour vaccines produced in situ by established genetically engineered bacteria" on the nature biological engineering.
Researchers have developed an oral cancer vaccine that activates a powerful anti-tumor immune response and immune memory effect in multiple preclinical tumor models.
Compared with traditional vaccination, oral vaccines are easier to take and most of the costs are lower. More importantly, oral vaccine activates the body's adaptive immune response by stimulating the immune cells in the intestinal tract. Since 70%-80% of the immune cells are distributed in the intestinal tract, this vaccine can produce a strong immune response. However, currently available oral vaccines are very limited.
In addition, there are two major challenges in the development of oral cancer vaccines: one is the harsh environment of the digestive tract, and the other is the complex intestinal epithelial barrier.
In this study, the researchers developed an oral glucose controlled bacterial robot for the production of tumor vaccines in the intestine, and designed a bacterial robot based on genetically engineered Escherichia coli, which can secrete outer membrane vesicles (OMV) carrying tumor antigens under the induction of arabinose.
Adventitial vesicles are natural mediators for the interaction between intestinal flora and the immune system. Together with tumor antigens, they can effectively penetrate the intestinal mucus and epithelial barrier, and are ingested by antigen-presenting cells in the lamina propria (a special mucosal layer).
OMV oral tumor vaccine derived from genetically engineered bacteria
In a mouse model, oral administration of arabinose and genetically engineered E. coli resulted in the production of outer membrane vesicles that pass through the intestinal epithelium into the lamina propria, where they stimulate dendritic cell maturation. In the mouse model of lung metastatic melanoma and subcutaneous colon tumor, the outer membrane vesicles carrying antigen inhibited tumor growth and protected animals from tumor re attack.
The results showed that oral vaccine activated strong anti-tumor immune response and immune memory effect in several preclinical tumor models, played an anti-tumor role in a variety of mouse cancer models, and significantly inhibited tumor growth.
Long term immune memory induced by oral vaccine
Initially, researchers focused on a report of bacterial enteritis caused by food contamination. It is speculated that if the pathogen can break through the biological barrier and trigger immune response, then the artificial engineered bacteria should be able to overcome the complex gastrointestinal environment. Inspired by this, researchers began to try to use bacterial robots to provide oral vaccines.
In short, this oral bacterial robot can controllably produce vaccines against a variety of tumors in mice with the help of genetic engineering technology. More importantly, it can be used as an antigen transmission and display platform to prevent infectious diseases and other diseases. It brings great hope for further development of oral vaccine.
Original source:
Yale Yue, et al. Antigen-bearing outer membrane vesicles as tumour vaccines produced in situ by ingested genetically engineered bacteria. Nature Biomedical Engineering, 1-12.
Article source:
https://www.medsci.cn/article/show_article.do;jsessionid=50873955EC048576DD2BE39CC5944183?id=d025e26734d1
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