Chapter 122: The Royal Swedish Academy of Sciences

Rosaline’s eyes widened.

“So?”

Young-Joon urged Rosaline for an answer.

—It is definitely a sci-fi novel full of imagination.

“Would it be too difficult?”

—Honestly, yes, it is. You’re throwing out these crazy, unbelievable ideas because you trust me, right?

“Yeah.”

—I didn’t think of that, but it’s interesting. It will be realistic if I improve the technical parts.

“Really?”

—Yes. Let’s make it together.

Rosaline said.

* * *

Kakeguni had practically given up on this year’s Nobel Prize. Honestly, he thought that it was going to go into Oliver’s hand, and he thought that his last chance had gone out the window because he was so old.

However, the tables had turned now. The immune checkpoint inhibitor had a fatal side effect: it was countereffective in patients who had a mutation in the EGFR gene.

‘Then won’t I have a chance?’

Kakeguni, who was in deep thought, received a phone call in his hotel room.

—There’s a guest who would like to meet you. Should I tell them to wait in the lobby?

The hotel employee at the front desk said.

“Yes. I’ll come down.”

Young-Joon had contacted Kakeguni today asking to meet briefly. He thought that it would obviously be Young-Joon, but it was someone entirely unexpected. It was a beautiful and intelligent woman who was in good shape and looked to be about thirty years old.

“Hello, professor. My name is Song Ji-Hyun, and I am from a Korean pharmaceutical company called Celligener.”

Song Ji-Hyun introduced herself.

“Nice to meet you. Were you in my lecture?” Kakeguni asked while shaking her hand.

“Yes. I was thinking about a lot of things after listening to that lecture, and I had a very good idea. I asked the staff at the conference and came to this hotel. I apologize that I asked to meet you so suddenly without contacting you in advance.”

“No, it’s alright. Should we go over there and continue?”

Kakeguni led Song Ji-Hyun to the coffee shop in the hotel and ordered a beverage.

“So, what is the good idea?” Kakeguni asked.

“There is something called chimeric immunotherapy among the technologies developed by Conson & Colson. A-Bio has acquired it and is currently progressing with further development. I think that if it continues to advance, it could soon conquer all types of cancer. I believe it could be the most powerful cancer treatment.”

Kakeguni nodded.

“I agree as well. Clearly, there is a reason why scientists are abandoning the old strategy of targeting cancer cells with chemicals and are trying to use the capabilities of the human immune system.”

“Because chemical agents can destroy normal cells, and it is easy for cancer cells with resistance to develop.”

“That’s right. If the patient relapses, the drug becomes useless, and it’s over for the patient. However, immunotherapy is not like that, especially chimeric immunotherapy. Theoretically, it can be upgraded endlessly.”

Chimeric immunotherapy was about attaching new weapons to immune cells. If cancer cells evolved to have armor when immune cells were given powerful swords? They would just have to give guns to the immune cells. If the cancer cells evolved further and wore bulletproof vests? They just had to give missiles to the immune cells. Being able to engineer immune cells meant that they could create them in the most optimized state to target cancer cells.

“Although it is currently unrealistic since it costs tens of billions of won and takes months of work,” Kakeguni said.

“That is what I am talking about,” Song Ji-Hyun said with sparkling eyes. “Professor, wouldn’t we be able to engineer the immune cells in the patient’s body using your dendritic cell manipulation technology?”

“With dendritic cell manipulation...?”

“Yes. Your technology is about using endocytic receptors to feed dendritic cells with the desired substance, right? And then we make the dendritic cell recognize that substance as an antibody and teach the immune cells to find and destroy it?”

Cancer cells had various kinds of mutations, such as an EGFR mutation. What would happen if they gave the EGFR mutation to the dendritic cell? The dendritic cell would analyze the EGFR mutation carefully, and then teach it to the immune cells.

‘This looks dangerous, so find this and destroy it.’

Dendritic cells were the commander of immune cells; the immune cells that received its orders would look for EGFR mutations furiously. There was a huge difference in the efficiency of an operation between having a command tower and not having one.

Kakeguni had developed a method to feed desired substances to dendritic cells. Of course, this process occurred naturally in the body even if it was not fed to them, but in extremely low probability. It sort of worked like this:

1. A floating dendritic cell meets a cancer cell due to luck.

2. That cancer naturally dies or gets destroyed by a wandering immune cell at that moment with incredible luck.

3. Out of the billions of substances that are flowing out of the cancer cell, the mutated EGFR miraculously gets absorbed into the dendritic cell.

4. This lucky single dendritic cell analyzes the mutated EGFR and survives until it can teach the immune cells.

It was not easy to successfully complete all these steps. The reason why it was so inefficient was because dendritic cells were originally a command tower to recognize foreign pathogens. They were extremely skilled in finding substances made by foreign bacteria that had entered the body.

However, it was not easy for them to track something like a mutated EGFR that a cancer cell made as it was originally the patient’s cell. But using Kakeguni’s technology, they could feed the mutated EGFR to many dendritic cells at once and make them recognize that as the enemy; the immune mechanism would be activated very efficiently.

“Hm...”

Kakeguni thought hard for a moment.

“What do you think? Do you think it’s a good idea? If it’s okay, should I talk to Mr. Ryu and start this project?” Song Ji-Hyun asked.

“Do you know Mr. Ryu?”

“... We are not closer personally, but we did a few projects together in the past.”

To be honest, Song Ji-Hyun was not very confident in this amazing idea. She did not know about dendritic cells or chimeric immunotherapy in as much detail as Kakeguni or Young-Joon. She could be just spewing an embarrassing delusion. However, that was why she came to Kakeguni first rather than meeting Young-Joon; it was so that she would be able to talk to Young-Joon more confidently if Kakeguni said it was possible.

At last, Kakeguni opened his mouth.

“However, Doctor Song, dendritic cells are commanders, not engineers. Dendritic cells can teach immune cells about who the enemy is, but they cannot edit immune cells themselves.”

“Would this be difficult?”

“Substances are delivered from dendritic cells to immune cells and the antibody that the dendritic cell recognized would probably move as well, like the mutated EGFR. But the EGFR is just something that controls cell growth. It can’t manipulate the immune cell’s genes or anything like that.”

Thud!

The coffee shop doors opened forcefully. The bell on the door rang loudly. Young-Joon, who was out of breath, walked inside while catching his breath.

“Professor Kakeguni!” he shouted as he ran towards them.

Kakeguni and Song Ji-Hyun were startled.

“... Doctor Ryu...?”

“Mr. Ryu...?”

Young-Joon briefly greeted Song Ji-Hyun at the table.

“Hello, Doctor Song.”

Then, he quickly turned to look at Kakeguni. He was flushed, and his face, which was more excited than ever, was filled with passionate joy.

“Professor, let’s use the dendritic cell technology. Let’s make chimeric immune cells with that!”

Song Ji-Hyun’s eyes widened.

“What a coincidence! Doctor Song was just talking about that,” Kakeguni said.

“Really?”

Young-Joon turned his face toward Song Ji-Hyun in surprise.

“Uh...”

Song Ji-Hyu blushed a little.

“But Professor Kakeguni said that it won’t work. He said that dendritic cells only give the substance that will become the antibody to the immune cell and that it can’t manipulate genes...”

“Let’s put in Cas9,” Young-Joon said.

The two froze like someone had slammed a hammer down on the table.

“Let’s attach an RNA that recognizes the target on Cas9, feed it to the dendritic cell, then deliver it to the immune cell. It will be recognized and delivered easier because it is originally from a bacteria,” Young-Joon said. “This process is not making the immune cell recognize and search for Cas9, you know that, right? Cas9 are gene scissors; it is to manipulate the immune cell’s genes with the Cas9 that has entered the cell.”

“Holy... Is that possible?”

Kakeguni was shocked.

“Doctor Ryu, a DNA particle is smaller than dust. Even if you use gene scissors, it is difficult to manipulate it, even in the lab. But you’re going to indirectly introduce it to the immune cell through another cell, and then manipulate those fine genes by cutting and gluing it within the body? By indirectly using the gene scissors through a cell?”

In terms of surgery, this was no different than performing brain surgery by holding a scalpel with a robot arm that was inside a claw machine; it was insane.

“Doctor Ryu, you think that will work?” Kakeguni said like it was ridiculous.

“It will. There's a way,” Young-Joon said confidently. “I will explain the details soon. Just tell me if you have a kit that can be put into a dendritic cell through endocytosis.”

“I... do have one...”

“That’s enough. I can guarantee you that we can safely manipulate more than forty gene locations in any way we want at once.”

“Forty!” Kakeguni shouted.

“Yes. If we use this, we can make chimeric immune cells very easily, and we can destroy most cancers at once.”

“...”

Song Ji-Hyun was completely frozen. She had almost given up on the idea with a little embarrassment when she heard Kakeguni’s answer. But Young-Joon was going to break through it in such a powerful way? Can this really work?

‘Wait.’

If this succeeded, what kind of world would open up? Chimeric immunotherapy was evaluated to have the potential to cure ninety percent of leukemia patients after it was developed.

‘...’

But that wasn’t all. The technology that could simultaneously manipulate forty genes of individual cells within the human body: this was DNA surgery. It was the same as a surgeon cutting open the abdomen with a scalpel, excising lesions, and administering medication, but on a molecular level instead.

Chills ran down Song Ji-Hyun’s body.

“Doctor Ryu, this makes no sense. Even if you can extract a patient’s immune cells and manipulate its genes in a test tube, you can’t manipulate forty of them,” Kakeguni criticized.

“That’s right.”

“Then how could you possibly handle forty genes when you are

indirectly

using another cell and

indirectly

manipulating their genes within their body, where there are millions of intricately linked variables?”

“It’s because it is done in the body,” Young-Joon replied. “As you know, immune cells cannot live long if you extract them outside the body. There is a limit to growing immune cells. The time constraint is why it is difficult to manipulate their genes outside.”

“...”

“But it is okay since we are doing it inside the body. Instead of laying the immune cell on the surgical bed, we are doing the surgery in the immune cell’s home. It is the most stable. The dendritic cell will deliver the information of about forty genes and Cas9 to the immune cell, and Cas9 will rip apart and fix the forty genes in the immune cell,” Young-Joon said. “That immune cell will become the most powerful cell in the history of mankind. Lung cancer cells will not stand a chance.”