Chapter 1078 Cast a Wide Net and Catch More Fish

Sanbo Hospital, the laboratory and Ruixing Company form a complete chain. With a complete chain, it is not difficult to develop a set of reagents for K virus antibodies, because the methods for detecting antibodies are similar and can be achieved with a few modifications.

Sure enough, antibodies to the K virus were found in Sisi's body. After multiple injections of the K virus in Sisi's body, it fought with the human immune system many times, allowing the immune system to find a way to target it, activate certain immune cells, and produce corresponding antibodies. The activation of immune cells and the production of antibodies killed the K virus not long after it was injected into the body.

Increasing the injection dose is one way, but this is limited. Increasing the injection amount of the virus regardless of the risk can easily over-activate the immune system, and the human body will collapse due to excessive immune response.

The failure of this experiment forced Yang Ping to review his experiment again. Scientific research is like this, constantly moving forward in trial and error. In fact, trial and error itself is accumulation, and the data of trial and error is a huge wealth of scientific research.

For example, wind tunnels are needed to study airplanes. In fact, using wind tunnels to blow airplanes is a process of trial and error. It constantly simulates the state of airplanes flying at high speeds, and then collects data. Based on the feedback data, the airplanes are constantly improved, and the airplanes are slowly modified to satisfaction.

Nowadays, many trials and errors in scientific research are completed by computer simulation, but computers can never perfectly simulate real scenes.

The K factor is the core of this experiment. Everything revolves around the K factor, and adenovirus is just a carrier. There is a huge flaw in the combination of K factor and virus this time, that is, the virus is always an alien pathogenic microorganism. It is impossible to stop fighting with the human body. In the process of fighting, both the immune system and the virus will continue to change, and this change is destined to be unstable.

Even if the original virus that has achieved certain success is used, the result is the same, because they belong to the same system, the fund structure is the same, and they are essentially the same virus.

Although oncolytic virus therapy also uses viruses, the virus is not used as a carrier, but as a marker. It can mark tumor cells and then cause the immune system to attack.

CAR-T cell therapy also uses immune cells to directly attack tumor cells. Can we learn from the way of CAR-T cells? Yang Ping pondered.

CAR-T cell therapy uses the body's own T lymphocytes to modify and then use them as weapons to attack tumors. It is a human immune cell itself. After entering the human body, there is no possibility of being attacked by the body's own immune system. The more it is injected, the more it will work.

However, CAR-T cells are currently very effective for blood tumors, and some tumors can be cured, but they are not effective for solid tumors because of the barrier effect of solid tumors, which prevents CAR-T from entering the interior of solid tumors. Later, based on CAR-T cell therapy, CAR-NK cell therapy was developed. This cell can break through the barrier of solid tumors, enter the interior of solid tumors, and hunt tumor cells.

CAR-T cells are chimeric antigen receptors based on T cells. This antigen receptor is equivalent to a positioning navigation device. It can specifically identify tumor cells in the body and release a large number of multiple effector factors through immune action. They can efficiently kill tumor cells, thereby achieving the purpose of treating malignant tumors.

The K factor discovered by Yang Ping is very special. It has the dual capabilities of navigation and attack, but it cannot reach the target tumor by itself, so whether it recognizes or attacks tumors, it relies on a vehicle.

What if NK cells were used as this vehicle? Yang Ping became more and more excited, and a lot of knowledge about NK cells emerged in his mind.

NK cells, also known as natural killer cells, are important immune cells in the human body. They are very powerful. According to current research, one NK cell can kill 27 tumor cells. It is the strongest and most effective immune cell against cancer cells and viruses. NK cells fight on the first line of defense to protect human health all year round. They can go directly to the battlefield to kill the enemy without being activated. Because of their alert response and broad spectrum of killing, they are often called the "special police" force in the immune army. They are the trump card of the human immune system.

The combat process of NK cells is very clear. When it encounters abnormal cells, it will stick closely to these cells, and then release a special protein called perforin, and some other toxins at the same time. Perforin and toxins work together, so toxins can drill into abnormal cells and cause them to die. In addition, NK cells also release various cytokines, which are like signals that can mobilize more immune cells to participate in the battle.

Normally, NK cells build a solid wall for the human body, detect and kill diseased cells in time, and effectively prevent cancer from happening, but it also fails for various reasons.

K factor not only has the function of killing tumor cells, but also can identify tumor cells. It has the dual functions of navigation and combat. If K factor is embedded in NK cells, then NK cells will have another weapon.

Since the human body is always worried about K factor after it combines with the virus and tries its best to deal with it, what about embedding K factor into NK cells? Just like embedding antigen receptors into immune cells, forming an artificially modified NK cell.

Yang Ping sorted out his thoughts, then summarized them, formed a complete plan, and called everyone to a meeting to discuss.

"We need to adjust our thinking and evolve into two routes. Continue research on K virus therapy, and open a new route to embed K factors into NK cells. Virus therapy and cell therapy go hand in hand. Professor Zhang, you are here to cooperate with Lu Xiaolu to continue K virus therapy. Therapy, Tang Shun's stem cell laboratory cooperates with Lu Xiaolu's tumor laboratory to start NK cell research. Professor Lu has a very heavy task, and you have to take on both tasks at the same time." Yang Ping assigned tasks on the spot at the seminar.

"Now let me do this project?" Professor Zhang was a little unbelievable. This is equivalent to moving from a supporting role to a leading position. How can there be such a good thing? K-Virus therapy has reached the current stage, even if it ultimately fails, this is It is a top topic in the world, not to mention that the possibility of final success is very high. The success mentioned here does not necessarily cure the tumor. As long as it is effective, it opens up a new path. In fact, it has already achieved success, and now it is just striving for greater success.

"Yes, you come and do it with Professor Lu." Yang Ping has no unnecessary nonsense. He has too many topics. For some topics, he can only do strategic planning and leave the specific implementation to them.

"Professor, I have always had great confidence in cell therapy. I believe that 90% of diseases in the future can be solved through cell therapy, while other treatment methods only account for 10%. In the future, the largest department in all hospitals will be cell therapy, and the rest will The departments are all small departments, and stem cells are only part of cell therapy. I recently I was thinking that we should expand the scope of our research and change the stem cell laboratory to a cell therapy laboratory. I didn't expect that the professor would directly assign me a task. Okay! We will start research tomorrow. Professor Lu and I are neighbors downstairs. , Cooperation is very simple. "Tang Shun has great enthusiasm for the tasks assigned to him by Yang Ping.

"In fact, the most valuable result of our research on tumor treatment is K factor. We should build a system around it and how to make it play its greatest role, instead of taking over the main role. It revolves around its vector virus, so we focus on it. , launched multiple research lines and decided to try all the possible combinations we thought."

"The treatment of K virus is not limited to the current treatment of this kind of tumor. Research on K virus treatment should also be carried out for other tumors. For example, whether the hepatitis virus can be genetically modified and combined with K factor to treat liver cancer, because the hepatitis virus affects liver cells. Highly selective invasion capability.”

Yang Ping feels that the advantages of weight loss K factor should be fully utilized. The prospects are very broad. We should cast a wide net, collect more fish, and select the best.

The K factor can even be split, that is, the warhead and navigation parts are separated and chimerized separately. Different combinations may obtain NK cells with different combat effectiveness.

"Dr. Tang and Professor Lu should be very familiar with NK cells. You have both engaged in research in this area. Please introduce them to everyone." Yang Ping named them two to introduce them to everyone.

"Let me tell you, I've done research on this before."

Tang Shun immediately took over the task.

"CAR-NK cell therapy can actually see the subsequent development of CAR-T cells. The sources of NK cells used for CAR-NK cell engineering include peripheral blood, umbilical cord blood, and established NK cell lines, especially the NK-92 cell line. , and human pluripotent stem cells. Compared with T cells, this wider potential source makes NK cells easier to obtain, and it is very easy for us who started with stem cells. "

"What exactly can NK cells do? There are many ways for activated NK cells to eliminate target cells, such as: releasing perforin and granzymes, causing target cell lysis or apoptosis; promoting FasL expression and inducing apoptosis; releasing tumor necrosis Factor-α, interferon-γ, granulocyte macrophage colony-stimulating factor, and chemokines, recruit and activate other effector immune cells; antibody-dependent cell-mediated cytotoxicity, etc., it has many methods, and Rather vicious.”

"Because of these means of attacking abnormal cells, CAR-NK is the most advanced field in applied research and clinical medical practice in recent years, and its clinical application in tumor immunotherapy is increasingly showing great potential."

"However, CAR-NK cell therapy also has its own shortcomings. For example, K cells have a short lifespan in the absence of cytokine support, resulting in limited persistence in the body. But there are now some methods to overcome this shortcoming: such as the use of cytokine armor; Structural optimization of CAR; other genetic modifications, etc.”

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"If K factor is embedded into NK cells, many of the shortcomings of NK cells can be very well avoided."

Most of the researchers here are Ph.D.s. The knowledge of Ph.D.s is not broad, but very deep in a certain field. This kind of depth is not accessible to ordinary people. The masters and undergraduates who participated in the discussion are now confused. They can understand every word, but they have no idea what it means when connected.

"Theoretically, embedding K factor into NK cells can give NK cells an unprecedented powerful armor, improve their survival rate, and accurately identify tumor cells. However, once K factor is integrated inside the NK cells, It cannot be released at all." Lu Xiaolu offered his own opinion.

Yang Ping understood his concerns. K factor has two killer features. One is that it can accurately identify abnormal cells, and the other is that it can start the apoptosis program of these cells. When K factor integrates with the virus, the virus can carry it into the tumor cells, and then it can function in the cells and start the apoptosis program.

Now let it integrate with NK cells. NK cells cannot enter tumor cells. They can only be outside the cells. In this way, it is unknown whether K factor can play a role. The K factor alone can play a role, but it may not be able to kill tumor cells when integrated with NK cells.

"Don't worry, even if it can't play a killing role, but only plays a recognition role, the value of this integration is also very large, and it can provide armor for NK cells and prolong the survival of NK cells. These two points are enough. NK cells themselves can release some of their own factors to start the apoptosis of tumor cells, so we don't need to be trapped in the original inherent thinking." Yang Ping told Lu Xiaolu.

Lu Xiaolu thought about it. Indeed, his thinking just now was still stuck on the experiment of K factor combined with adenovirus, because adenovirus does not have the ability to start the apoptosis of tumor cells, but it has the ability to infect tumor cells, so K factor must be used to kill tumor cells. Now the combination of K factor and NK cells is completely different.

"Since this experiment failed, Sisi's experiment should be temporarily stopped." Song Zimo suggested.

Yang Ping nodded: "Pause."

This kind of high-level discussion can only be limited to a few people. The rest of the people are confused. They only hate that they have not read much and can't understand a few words.

After the meeting, Yang Ping started drawing pictures on a piece of white paper in the office, trying various combinations between K factor and NK cells. Sometimes, thinking must be expressed in pictures, and words can't express it at all. For example, the chimera of K factor and NK cells, where exactly is the chimera, how is the chimera, and to draw their simple genetic map, this situation can't be expressed in words. For scientific research, image thinking is very important.

The ocean of knowledge is boundless. If a person can truly understand the knowledge of a narrow professional range, he can achieve outstanding results. If someone can make a little innovation on the basis of understanding, then this person is at the level of winning the Nobel Prize.

Yang Ping has understood almost all of this medical knowledge, so it is relatively easier for him to use this knowledge to innovate than others. For example, the combination of K factor and NK cells requires the integration of several disciplines, and these disciplines must be understood.