godfather of surgery

Chapter 1078: Cast a wide net and catch more fish

Sanbo Hospital, 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 of detecting antibodies are similar and can be achieved with slight modifications.

Sure enough, antibodies to the K virus were found in Sisi's body. After the K virus was injected multiple times into Sisi's body, it fought against the human immune system many times, allowing the immune system to find a way to target it, activating certain immune cells and producing 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 solution, but this is limited. Increasing the injection dose of the virus without considering the risks can easily over-activate the immune system, causing the body to collapse due to excessive immune response.

The failure of this experiment forced Yang Ping to review his experiment again. This is what scientific research is all about, constantly moving forward through trial and error. In fact, trial and error itself is accumulation, and the data from trial and error is a huge asset for scientific research.

For example, studying airplanes requires a wind tunnel. In fact, using a wind tunnel to blow up an airplane is a process of trial and error. It constantly simulates the state of an airplane flying at high speed, and then collects data. The airplane is continuously improved based on the feedback data, and the airplane is slowly modified to a satisfactory level.

Nowadays, a lot of trial and error in scientific research is done using computer simulation, but computers can never perfectly simulate real-life scenarios.

The K factor is the core of this experiment. Everything revolves around the K factor, and the adenovirus is just a carrier. There is a huge flaw in the combination of the K factor and the virus. That is, the virus is always a foreign pathogenic microorganism, and its struggle with the human body cannot be stopped. In the process of the struggle, both the immune system and the virus will continue to change, and this change is destined to make it unstable.

Even if we use a virus that has already achieved a certain degree of success, the result will be the same, because they belong to the same lineage and have the same fund structure. In essence, they are still the same virus.

Although oncolytic virus therapy also uses viruses, the viruses are not used as carriers but as markers. They can mark tumor cells and then induce the immune system to attack.

CAR-T cell therapy also uses immune cells to directly attack tumor cells. Can we learn from the CAR-T cell approach? 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. CAR-T cell therapy is a human immune cell and there is no possibility of being attacked by the body's own immune system after entering the human body. The more cells injected, the more effective they will be.

However, CAR-T cells are currently very effective against blood tumors, and can cure some tumors, but they are not very effective against solid tumors because of the barrier effect of solid tumors, which prevents CAR-T cells from entering the interior of solid tumors. Later, based on CAR-T cell therapy, CAR-NK cell therapy was developed. This type of 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 and navigation device that can specifically identify tumor cells in the body and release a large number of multiple effector factors through immune action. They can effectively 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 is identifying or attacking the tumor, it relies on a vehicle.

What would happen 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 into battle and kill enemies directly without being activated. Because of their alert response and broad-spectrum killing ability, they are often called the "special police" force in the immune army. They can be called the trump card of the human immune system.

The combat process of NK cells is very clear. When they encounter abnormal cells, they will stick to these cells tightly, and then release a special protein called perforin, and some other toxins at the same time. Perforin and toxins work together, so the toxins can drill into abnormal cells and cause them to die. In addition, NK cells will 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 a timely manner, thereby effectively preventing the occurrence of cancer, but they sometimes fail for various reasons.

The 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 fighting. If the K factor is embedded in NK cells, the NK cells will now have an additional 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, an artificially modified NK cell is formed.

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

“We need to adjust our thinking and advance along two routes. We will continue to study K virus therapy and open a new route to embed K factor into NK cells. Virus therapy and cell therapy will go hand in hand. Professor Zhang, you will work with Lu Xiaolu to continue with K virus therapy, and Tang Shun’s stem cell laboratory will cooperate with Lu Xiaolu’s tumor laboratory to start NK cell research. Professor Lu’s task is heavy, and you will have to take on tasks on both sides at the same time.” Yang Ping assigned tasks on the spot at the discussion meeting.

"You're going to let me do this project now?" Professor Zhang found it hard to believe. This was equivalent to him moving from a supporting role to a leading position. How could such a good thing happen? K virus therapy has come to the current stage. Even if it fails in the end, it is still a world-class project. What's more, the possibility of success in the end is very high. The success mentioned here does not necessarily mean curing the tumor. As long as it is effective, it has opened up a new path. In fact, it has already been successful. Now it is just a matter of striving for greater success.

"Yes, you and Professor Lu can do it." Yang Ping didn't say any extra words. He had too many projects. For some of them, he could 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 can be treated by cell therapy in the future, while other treatment methods will only account for 10%. In the future, the largest department in all hospitals will be cell therapy, and the rest will be small departments. Stem cells are only a part of cell therapy. I have been thinking recently that we should expand our research scope and change the stem cell laboratory into a cell therapy laboratory. I didn't expect you to assign me a task directly. Okay! We will start the research tomorrow. Professor Lu and I are neighbors living upstairs, so cooperation is very simple." Tang Shun was very enthusiastic about the task assigned to him by Yang Ping. "In fact, the most valuable research result of our research on tumor treatment is the K factor. We should build a system around it, how to make it play the greatest role, rather than overshadowing it, and around its carrier virus, so we take it as the center and develop multiple research routes, and decide to try all the possible combinations we think."

"The treatment of K virus is not limited to the current treatment of this type of tumor. Other tumors can also be studied by K virus treatment. For example, genetic modification of hepatitis virus and combination with K factor can be used to treat liver cancer, because hepatitis virus has a high degree of selective invasion ability to liver cells."

Yang Ping thinks that the advantages of K factor in weight loss should be fully utilized, and the prospects are very broad. We should cast a wide net, catch more fish, and choose the best ones.

It is even possible to split the K factor, that is, to separate the warhead and the navigation unit and integrate them separately. Different combinations may produce NK cells with different combat effectiveness.

“Dr. Tang and Professor Lu should be very familiar with NK cells. You have both conducted research in this area. Can you introduce them to everyone?” Yang Ping called on them to introduce themselves to everyone.

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

Tang Shun immediately took over the task.

"CAR-NK cell therapy can actually be seen in the subsequent development of CAR-T cells. The sources of NK cells used for CAR-NK cell engineering include peripheral blood, umbilical cord blood, 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. For us who started with stem cells, it is very easy to obtain NK cells."

"What can NK cells do? There are many ways for activated NK cells to eliminate target cells, such as: releasing perforins and granzymes, leading to target cell lysis or apoptosis; promoting FasL expression, inducing cell apoptosis; releasing tumor necrosis factor-α, interferon-γ, granulocyte macrophage colony-stimulating factor, and chemokines, recruiting and activating other effector immune cells; antibody-dependent cell-mediated cytotoxicity, etc. It has many means and is quite toxic."

"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 now there are some ways to overcome this shortcoming: such as using cytokine armor; structural optimization of CAR; other genetic modifications, etc."

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

Most of the researchers present here are PhDs. PhDs do not have broad knowledge, but rather very deep knowledge in a certain field. This depth is not accessible to ordinary people. The masters and undergraduates who are participating in the discussion as auditors are now completely confused. They can understand every word, but they have no idea what it means when they are connected together.

“In theory, embedding K factor into NK cells can give NK cells an unprecedentedly strong armor, improve their survival rate, and accurately identify tumor cells. However, once K factor is integrated into NK cells, it cannot be released at all.” Lu Xiaolu put forward his own insights.

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

Now let it integrate with NK cells. NK cells cannot enter the tumor cells, they can only be outside the cells. So it is unknown whether the 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 cannot kill and only plays a recognition role, the value of this integration is also very great. Moreover, it can provide armor to 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 initiate 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 mind was still stuck on the experiment of combining K factor with adenovirus. Because adenovirus does not have the ability to initiate 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 has failed, let's stop Sisi's experiment for the time being," Song Zimo suggested.

Yang Ping nodded: "Pause."

This kind of high-end discussion can only be limited to a few people, while the rest of the people are confused and only regret that they have not read enough and cannot understand a few words.

After the meeting, Yang Ping started drawing on a piece of white paper in his office, trying various combinations of K factor and NK cells. Sometimes, thinking must be expressed in pictures, and words cannot express it at all. For example, the chimera of K factor and NK cells, where and how they are chimerized, they need to draw their simple genetic map. This situation cannot be expressed in words. For scientific research, visual thinking is very important.

The ocean of knowledge is boundless. If a person can truly understand the knowledge in a narrow professional scope, he can achieve outstanding results. If someone can make a little innovation based on his 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 crossing several disciplines, and these disciplines must be understood.