Chapter 121: The Royal Swedish Academy of Sciences (8)

Samuel, the editor for

Science

, was extremely excited after reading the newsletter that he received in the morning.

Jessie! Jessie! Go on a work trip! he shouted urgently.

To Korea? Jessie, who had basically become Young-Joons personal interviewer, asked.

No. Sweden.

Oh! What a surprise! Is it Karolinska? Or Lund University? Doctor Ryu Young-Joon has been dominating the scientific community these days, so its time for a paper to come out from the West as a counterattack. Jessie said like she was glad to hear it.

Its Doctor Ryus.

What?

Jessie squinted.

Doctor Ryu took his scientist to a conference in Sweden, and he wrote a paper in two weeks after doing research there.

... How is that possible?

Has anything hes done ever made sense before? Anyways, go. This is important.

Has anything hes done not been important? Jessie said, impersonating Samuel. Did he make some incredible new drug again? she asked as she approached him.

He reported on the countereffect of the immune checkpoint inhibitor.

Immune checkpoint inhibitor?

Doctor Olivers technology was developed at the Cold Spring Lab.

...

The most famous technology among the next-generation of immunotherapies. Its about how hyperprogression can occur if it is administered to lung cancer patients with an EGFR mutation.

Hyperprogression? Jessie said. She was shocked. This isnt just a mere side effect.

I know. Its not a side effect; its a countereffect. And I think there should be some additional explanations about the paper. This paper was the paper that

Nature

emphasized the most two years ago. And its also what the Cold Spring Lab and Jamie Anderson put forward as their biggest achievement in recent years.

...

The scientific community might exchange some bitter words with each other. Jamie Andersons faction and the opposite group might fight with Doctor Ryu in the middle of it.

Ill go, Jessie said.

* * *

Hyperprogression occurred in all the mice that were given more than one hundred micrograms of the immune checkpoint inhibitor. The mice that only received trace amounts were not in fatal condition, but they had gotten worse. The mice that received more than one milligram of the drug did not survive for more than eight days. As these mice all got worse than the mice that received no treatment, it seemed clear that the inhibitor was what killed the mice. This data was an important target for security as the paper hadnt been released yet.

However, Young-Joon revealed this to Hariot and the other evaluators, as well as Oliver and Kakeguni. He gathered them into a small seminar room and presented the data.

As you can see, hyperprogression occurred in all but four mice, which had received less than a microgram of the drug, and most died, Young-Joon presented.

He presented the data measuring the size of the mices tumor and their weight change. It was clear that the change in the tumor size was related to the dosage of the immune checkpoint inhibitor. Hyperprogression occurred faster with more of the inhibitor, the tumor enlarged more rapidly, and the mice died faster as a result.

I was told that this lung cancer cell was obtained from a lung cancer patient at Karolinska twenty years ago, Young-Joon said. What would have happened if the immune checkpoint inhibitor was administered to that patient? This drug is dangerous for NSCLC patients who have EGFR mutations.

The scientists were silent. Hariot was incredibly baffled. Hyperprogression really occurred, just like Young-Joon said. At this point, it was not science, but a prophecy.

So how does the hyperprogression occur? Can you tell us the mechanism? one of the doctors asked.

Yes, of course. We identified the mechanism as well. Lets look at the next data.

Young-Joon went on to the next slide.

As you can see, we identified that the expression of EGFR was amplified. If you treat these types of cancer cells with the immune checkpoint inhibitor, the EGFR signal becomes stronger, causing the cancer to increase explosively.

Doctor Ryu, Jamie Anderson said. The immune checkpoint inhibitor was administered to a lung cancer patient at Karolinska University Hospital.

Young-Joons eyes widened.

What? What kind of lung cancer?

It was NSCLC, like the one you wrote about.

...

Professor Marcus here is in charge of that patient. Professor, please explain it yourself.

A lung cancer specialist who looked to be in his sixties opened his mouth solemnly.

The patient is eighty-eight years old and has stage three lung cancer. No other treatments worked, and the commercialized immune checkpoint inhibitor was the only hope. We were going to use it anyway, so we consulted Professor Oliver, the developer of the treatment, since he was here, said Marcus. Of course, we dont know if theres an EGFR mutation in his lung cancer; we will know when we check it with the DNA analysis machine. We dont know whether hyperprogression will happen when there is a mutation in the EGFR like you said.

...

But thankfully, there are no signs of that yet. The sure thing is that the cancer is disappearing from the patients body. It has shrunk to about half its size.

...

Young-Joon was pale.

Ahem. Jamie Anderson cleared his throat after Marcus stopped talking and added, Doctor Ryu, the immune checkpoint inhibitor is a good drug. It can treat various types of cancer effectively, and lung cancer happens to be

Stop the administration right now! Young-Joon shouted. What have you done? You knew that I was studying that drug, didnt you? Even if there was no other way, how could you administer a drug that has issues with hyperprogression? You could have waited for the results! Or examined his EGFR!

The tumor shrunk to half its size!Jamie shouted. Doctor Ryu! I dont know how you got that data from the mice experiments, but the immune checkpoint inhibitor has gone through a strict clinical trial and has been approved by the FDA! There are no side effects, and it is clearly suppressing the growth of the tumor!

Most NSCLCs have EGFR mutations! Young-Joon said as he slammed the table with his fist. Professors, hyperprogression does not occur right away. In the beginning, the tumor shrinks due to the immune checkpoint inhibitor.This chapter was originally shared via n(0)vel(b)(j)(n).

Young-Joon opened other data on his computer. It was data from the first three days. The tumor was getting significantly smaller. However, it returned to its original size on day four, and it became enormous by day five.

The growth suppression early on is like an incubation period. The cancer cells in the tumor that received the inhibitor begin to express EGFR in large quantities. It just takes time to make it! The tables turn from the moment it gets produced! The size of the tumor doubles every six hours! Marcus and the other scientists looked confused. Frustrated, Young-Joon ran down from the podium.

Where is that patient right now? Lets examine their EGFR first.

...

Lets go, Doctor Ryu. I will show you the diagnostic imaging data, Marcus said.

* * *

The medical team and scientists followed Marcus into the CT room.

Look.

Marcus opened the files saved on his computer. It was a computed tomography scan[1] of the patients lung cancer. The tumor was as big as a fist in old scans, but it had shrunk to almost half its size in the scans Marcus showed Young-Joon next.

These were taken yesterday morning, Marcus said. What do you think, Doctor Ryu?

...

Young-Joon could not tell right now. If the patient was lucky, he may not have a mutation in his EGFR and be cured. But if he had an EGFR mutation? It might already be out of hand, as there was always calm before a storm.

Click.

The door to the CT room opened, and a young doctor appeared with a few nurses. An old patient, who was in a gurney, came with them.

Oh, Professor Marcus, the doctor said like he was happy to see him. I just contacted you because your patient complained about stomach aches and nausea. Did you come down here for that?

... A stomachache and nausea? Its the first I am hearing of this

Marcus was confused. The patient who was lying on the gurney was the NSCLC patient who was given the immune checkpoint inhibitor.

I see. I decided to take a CT scan and brought him here. What would you like to do?

Lets take a CT, Marcus said.

The patient had already received a contrast medium. He climbed into the CT machine and laid down on the bed. The machine began working and soon, a scan appeared on the monitor.

Clack.

Marcus dropped his pen. Shock swept over the medical team and the scientists. The tumor, which had shrunk by fifty percent, had grown bigger than its original size in just one day.

How How could this Marcus stuttered.

Its hyperprogression.

Young-Joon sighed.

* * *

Jessie, who had arrived in Sweden, had not been able to meet Young-Joon.

Im sorry, but now is not the time for an interview nor am I in the mood. There are a total of three co-first authors of this project, so please interview them, Young-Joon said briefly and declined the interview.

He was sitting in a small cafe in Solna and drinking coffee.

Do you want to save the patient?

Yeah, Young-Joon replied in a quiet voice.

That patient does not have much time left. Hyperprogression has already begun, and it is difficult to control it. He will probably die in a few days.

Is there any way?

Of course, I can think of countless ways.

Rosaline said like it was not a big deal.

But realistically, most of them will be difficult for me to do, right?

Most of them are illegal. For example, you could administer a large amount of EGFR inhibitor through inhalation to stop hyperprogression.

Theres an inhibitor like that?

You have to make it.

But it takes time to make it?

Thats why it is a problem. You will be able to save the patient if you borrow or steal a lab in Solna, organically synthesize the inhibitor, skip all the animal experiments and the clinical trial approval process, and then shove it into the patients nose.

Experimental treatment is possible if I get consent from Marcus and the patient, but they wont agree to use some unknown chemical that hasnt been tested before.

Wont they just trust you and let you do it since youre a miracle-working scientist who has been successful in a lot of things?

Well, maybe if I desperately try to convince them. But I dont want to try it with some unclear possibility that they might let me do it.

Just administer it secretly. Then, you can still save the patient.

But then Ill go to jail.

Rosaline thumped her feet on the ground in anxiety while sitting in the chair.

Then there is no way.

...

Its possible to use chimeric immunotherapy, but it takes too long.

Young-Joon was lost in thought, but then his eyes widened.

Wait. Chimeric immunotherapy

What about it?

Rosaline. Im going to write a sci-fi novel right now. Tell me the possibility of it working.

Alright. Tell me.

Chimeric immunotherapy takes out the immune cells and gives it a new weapon by editing the genes.

Yes.

And the dendritic cells are cells that provide information about cancer cells to immune cells. And Professor Kakegunis technology is about stimulating dendritic cells to help that process.

Thats right.

What if we revise it a little and make it so that the dendritic cell delivers the gene to the immune cell? What if we give the weapons to the immune cells in the patients body? Young-Joon asked. Then, wouldn't we be able to skip the process of extracting immune cells from the patients body and manipulating the gene and do the chimeric immunotherapy right away?

1. more commonly known as a CT