New research modifies E. coli to deliver antigens to activate immune responses

Oral tumor vaccines are becoming a reality

Compared with injectable vaccines, oral vaccines have three main advantages: the activated immune response may be stronger; mucosal immunity can be activated; compared with injections, oral methods are much more convenient, popularize vaccination faster, and people's compliance It is more sexual and does not require professional vaccinati.

Recently, in a study published in the sub-journal of "Nature", Chinese scholars designed a bacterial-derived oral tumor-like vaccine by genetically engineering Escherichia coli, which was shown in a variety of mouse models of canc.

What is an oral tumor vaccine? What are the advantages of oral tumor vaccines and what problems can they solve for patients? A reporter from Science and Technology Daily interviewed Nie Guangjun, one of the leaders of the above-mentioned research team and a researcher at the National Nanoscience Center of the Chinese Academy of Scienc.

Oral vaccines have obvious advantages but are difficult to develop

"The sugar pill vaccine I ate as a child is actually an oral vaccine against pol.

Compared with injectable vaccines, oral vaccines have three main advantag.

First, the magnitude of the immune response activated by oral vaccines may be strong.

"Theoretically, the greater the number of immune cells stimulated by the vaccine, the stronger the activated immune response will be, and the stronger the protective effect on the body will be in the e.

"Of course, excessive activation of the immune system is also a potential risk, so preclinical research and clinical trials are needed to determine the dose of oral vaccines to ensure that the immune response is within the range that the body can tolera.

Secondly, oral vaccines can activate mucosal immunity and stimulate the body to produce a special antibody IgA, which is mainly distributed in mucosal parts, such as the digestive tract and respiratory tra.

"However, for oral tumor vaccines, the significance of this mucosal immunity remains to be further studied and explor.

Furthermore, oral vaccines also have certain advantages in practical applicati.

"But oral vaccines are far more difficult to develop than injectable vaccines, and face more challenges," said Nie Guangj.

According to Nie Guangjun, his research group has long been concerned about the use of nanotechnology and biotechnology to develop new methods for the treatment of tumo.

Making 'bacterial robots' overcome two challenges

Nie Guangjun told reporters that there are two main challenges in the development of oral vaccines: First, vaccines need to overcome the complex digestive tract environme.

How to overcome these challenges? The answer is to create "bacterial robot.

Nie Guangjun told reporters that the research team genetically modified Escherichia co.

The genetically modified Escherichia coli can produce and secrete a vesicle with tumor antigens - bacterial outer membrane vesicle (OMV) in the intesti.

Like a truck, it will bring the loaded tumor antigens to the vicinity of immune cells under the intestinal epithelial barrier, thereby delivering these tumor antigens to the immune system and activating the anti-tumor immune response in the bo.

Nie Guangjun's team called the.

coli bacteria that work autonomously in the body according to their design "bacterial robot.

"Bacterial robots" are the core components of oral tumor-like vaccines, which can continuously generate OMVs with tumor antigens in the intesti.

On the one hand, it will cause the body's immune response to resist the tumor, but on the other hand, constant immune stimulation will also lead to immune exhaustion and toleran.

In order to eliminate this hidden danger, the researchers added a "responsive switch" to the tumor antigen ge.

With this switch, the "bacterial robot" can only carry out the tumor antigen gene in the presence of arabinose (a sugar substanc.

expressi.

In this way, the intestinal behavior of the "bacterial robot" can be controlled by oral arabinose, so that it will not get out of contr.

In animal model experiments, the researchers gave the mice some "sugar water" to drink after 24 hours of oral administration of the "bacterial robo.

The use of oral "bacterial robots" to generate OMVs with tumor antigens in situ in the gut not only solves the insurmountable problem of the epithelial barrier, but also overcomes the difficulties brought by the complex digestive tract environme.

"Initially, we adopted the way of direct oral administration of OMV, but found that OMV could not reach the intestinal site efficiently, so we considered the way of oral 'bacterial robo.

Because, compared with OMV,.

coli itself is a colony of intestinal flora, The tolerance is high.

" Nie Guangjun sa.

"However, the survival time of these 'bacterial robots' in the intestine is limit.

" Nie Guangjun told reporters that according to their observations, after 72 hours of oral administration, these "bacterial robots" will be excreted or degraded; in addition, Without the sugar arabinose, the "bacterial robot" behaves like other symbiotic bacteria in the g.

"From the perspective of animal experiments, this 'bacterial robot'-based oral tumor-like vaccine has no obvious side effec.

The situation in the human body needs further verificati.

" Nie Guangjun sa.

Talking about the suitable groups of oral tumor vaccines, Nie Guangjun said: "From the experience of oral polio vaccine, the vast majority of people can receive oral vaccin.

Of course, oral polio vaccine is to prevent diseases, and The oral tumor vaccine we are going to do is used to treat diseases, and the user is the patie.

We must strictly control the dose of the vaccine according to the patient's tolerance to the vacci.

Whether there are specific groups of people who are not suitable for oral vaccines, Further research is needed to verify .

”

Tumor vaccine is an important means to realize individualized treatment

With the development of the times, the concept and means of anti-tumor are constantly improvi.

The initial surgery, radiotherapy, chemotherapy and other methods are all a kind of treatment for most patients, which belongs to "brutal treatmen.

Later, precision treatment represented by targeted therapy was developed, which is a drug for a small number of patien.

"In the past 10 years, the voice of individualized treatment has been increasing, that is, each patient can correspond to a treatment meth.

" Nie Guangjun believes that tumor vaccine is a very promising individualized treatme.

"Because the gene mutations of tumor cells in each patient are different, that is, the tumor antigen information is uniq.

The tumor vaccine made by using these patients' unique tumor antigens is only applicable to the patient himself, a real individu.

Nie Guangjun believes that withthe development of antigen identification methods and delivery technology, tumor vaccines will definitely be used in clinical treatment, and relying on technological progress and the corresponding support provided by medical insurance policies, the cost of individualized treatment of tumors will also be greatly increas.

low.

Nie Guangjun predicts that the clinical application of injectable tumor vaccines will become a reality in the next 2-5 yea.

"Oral tumor-like vaccine is still a new technology, and it takes time to develop and optimi.

We are confident that in the near future, oral tumor-like vaccine can become a killer for mankind to defeat malignant tumo.

" He sa.

Nie Guangjun said that the next work of the research group mainly focuses on two aspects: first, to further improve the oral vaccine system based on "bacterial robots", to verify the effect in more tumor antigens and models, and to accelerate its transformation and implementation; second It is to use "bacterial robots" to try to transport vaccines and even drugs for other diseases, such as vaccines against gastrointestinal pathogenic microorganisms, drugs for enteritis, e.

, to further expand its application sco.