Passed by the Nobel Prize, and now Chen Lieping has raised 65 million yuan for new start-ups, how he sat on the "cold bench" step by step

introduction

On October 24, 2022, a biotechnology company called Normunity, founded by Chen Lieping, announced the completion of a $65 million Series A financing
.

The startup's goal is to develop antibody drugs to normalize immunity against cancer's escape of the immune system to treat "cold tumors"
that immunotherapy can't reach.

In 2018, Professor Chen Lieping regrettably passed by the Nobel Prize in Physiology or Medicine, not only to open up a new field of research in the field of immunotherapy, but also to translate these discoveries into applications
.

What kind of growth experience this outstanding immunologist has and what contributions he has made in the field of tumor immunity, this article will explain
it for you in depth.

Normunity is a combination
of the words "normal" and "immunity.
" Normunity is not to develop new immune checkpoint inhibitors, nor to develop bispecific antibodies or cell therapies, but to use antibodies to break down the barriers between the immune system and tumor treatment, normalize the immune system, and solve the problem that T cells cannot enter "cold tumors", thereby exerting anti-cancer effects
.

Chen Lieping proposed a new conceptual framework for cancer treatment
.
So, what is immune normalization? Should the fight against cancer be immune booster or immune normalization? What kind of growth experience does he have and what contributions have he made in the field of tumor immunity? This article will explain
each of them.

01

Chinese Pie

In 2018, when Yu Honjo and Allison won the Nobel Prize, Chen Lieping missed the opportunity
.
But what he brought to cancer treatment was far more important
than a Nobel Prize.

In December 1977, the door to the college entrance examination, which had been closed for more than ten years, opened again, and 5.
7 million candidates poured into the examination room
.
The torrent of the times has finally brought hope, and the cold winter is about to pass
.
In the spring of the following year, lucky students entered institutions of
higher learning.
In the torrent of this era, Chen Lieping also seized the historical opportunity and was admitted to Fujian Medical University
from the rural area where he cut the queue.
This year, Chen Lieping was 21 years old
.

When Chen Lieping entered the university year and the Sino-US Communiqué on the Establishment of Diplomatic Relations between China and the United States was issued, China's door to the world was suddenly opened
.
US President Jimmy Carter actively promoted the normalization of Sino-US diplomatic relations, laying the foundation
for Chinese scholars to study in the United States.
Thanks to this, Chen Lieping was able to successfully go to the United States for further study
.
Carter also did not expect that more than 40 years later, his advanced melanoma would be cured thanks to Chen Lieping's research
.

The fascinating thing about life is that it is unpredictable
.

In the summer of 1982, Chen Lieping graduated from Fujian Medical University and was assigned to the oncology department as a doctor
.
This young man was the captain of the school basketball team, loved sports and was full
of initiative.
Since he came to the front line, he has been determined: "I want to be a medical and saving oncologist
.
" "But in the 80s of the 20th century, tumor treatment was very backward, only a few chemotherapy drugs were available, and the toxicity was huge
.
Chen Lieping witnessed patients suffering from cancer treatment and left
one by one in pain.
There was a deep sense of powerlessness that slowly grew
in his heart.

Chen Lieping thought to himself: "I see this every day, but I can't do anything, and then watch the patient die, it's really frustrating
.
" ”

How can we change the status quo? After struggling to persuade his family, Chen Lieping resolutely resigned from the "iron rice bowl"
of the doctor.

He doesn't know where the future holds, but he believes that only when the overall level of awareness of cancer improves, doctors will be able to provide better drug treatment
to patients.

In 1983, Chen Lieping was admitted to Peking Union Medical College as a graduate student
.
His specialty is tumor immunology, where he studies how macrophages (the scavengers of the immune system) phagocytose cancer cells
.
Most of the students are from comprehensive universities, with solid foundation and vigorous
vitality.
Chen Lieping realized that among the group of classmates, he was relatively old
.
Therefore, he especially cherishes the hard-won opportunity to study, usually does not talk much, but is extremely diligent and focused
.
Even on cold winter nights, he often ran to experiments
.
Since then, he has focused on tumor immunology
, regardless of how the environment changes.

Heaven rewarded hard work, and Chen Lieping began to publish papers
after two or three years of admission.
At that time, their articles were mainly published in academic journals within the Chinese system, such as Chinese Immunization and Chinese Medicine
.
Industry insiders call these publications "Chinese School"
.
Chen Lieping, who came from the Chinese school, was not satisfied with the status quo and had the idea
of studying abroad.

In 1986, Chen Lieping applied to the United States as a visiting scholar, and then transferred to a doctoral degree
.
As the old saying goes, stand at thirty
.
Chen Lieping only started his doctoral studies at the age of 30, and it is not easy in a foreign country with completely different cultural habits
.
He admits: "After all, they are used to the social culture they grew up in, and most people will feel uncomfortable
for at least five years after moving to a new country.
" ”

In 1990, when Chen Lieping received his doctorate at Drexel University, he was stuck in a difficult choice
.
Standing at the crossroads of life, there are always many choices, and choice means paying an opportunity cost
.
Chen Lieping is also very entangled: stay in academia to continue to do basic research, go to the medical field to become a doctor, or go to the industry to do translational research?

02

The era of targeted therapy is on the rise

In 1990, Chen Lieping went to Seattle alone and joined the famous pharmaceutical company Bristol-Myers Squibb.

At Bristol-Myers Squibb, Chen Lieping began cutting-edge research
in tumor immunology.
In 1992, Chen Lieping published a paper in the top journal "Cell", and has since emerged
.
Chen Lieping introduced the ligand B7 of CTLA-4/CD28 into tumor immunity for the first time, and found that activating the immune response can clear tumors
.
This innovative work has opened up a new field of immunoagonist treatment of tumors and has also inspired follow-up research
on CTLA-4 antibodies in the treatment of cancer.

At Bristol-Myers Squibb, Chen Lieping is mainly engaged in the research of immune enhancement, which is like "stepping on the accelerator"
for immune cells.
However, this "throttle" is easy to step on the head, inducing immune "car accidents"
.
What's more, cancer patients themselves have a complete immune system, why do they have tumors?

Chen Lieping kept thinking, and suddenly at a certain moment, a flash of light: "Not all immune cells have problems, but the tumor will produce immunosuppressive mechanisms in its microenvironment?" "The tumor microenvironment is the "soil"
on which tumors depend.
As early as 1889, Stephen Paget proposed the "seed and soil" hypothesis, believing that cancer cells are "seeds" and the tumor microenvironment is the "soil"
that supports the development and growth of tumors.

Therefore, Chen Lieping proposed a new hypothesis: there are "immune escape molecules"
in the tumor microenvironment.
These molecules can blind the immune system and help tumors escape the immune system
.
What exactly are immune escape molecules? This idea drove Chen Lieping to delve into the tumor microenvironment to find answers
.

But at this time, the era of tumor treatment has changed
dramatically.

In the 90s of the 20th century, tumor genomics was on the rise
as humans gradually revealed the pathogenesis of cancer at the genetic level.
Oncologist declares: "As long as we understand the driving genes of cancer occurrence and progression, and design corresponding drugs in a targeted manner, we can specifically suppress cancer
.
" "This wave is turning into a clinical revolution
in targeted therapies.

Instead of testing compounds aimlessly, pharmaceuticals develop solutions
for specific oncogenic "targets.
" In the mid-90s of the 20th century, imatinib (Gleevec) was very successful in treating chronic myeloid leukemia, and ninety percent of patients could control their cancer
by taking medicine.
Imatinib can accurately act on the pathogenesis of cancer cells, and its emergence represents the arrival
of the era of precision therapy.
Since then, major pharmaceutical companies have turned to small molecule targeted drugs, and the research and development of "tinib" drugs has turned red and purple
.
"Tinib" is a small root, which represents "where to hit", this kind of small molecule targeted drugs, gradually become the "darling"
of major pharmaceutical companies.

In the spring of 1997, the weather in Seattle was warm and cold
.
Bristol-Myers Squibb leader told Chen Lieping: "The company has decided to close the entire tumor immunotherapy research and development department
.
If you choose to stay, you will have to give up tumor immunity research and engage in the research and development
of small molecule drugs.
"Under the torrent of the times, too much helplessness
is masked.
Although the mainstream has snubbed tumor immunology, Chen Lieping is unwilling to follow the trend, and he sticks to his interests
.
Years later, Bristol-Myers Squibb realized what
it had lost.

In desperation, Chen Lieping moved to the Mayo Clinic to silently explore the dawn of tumor immunity
.
The Mayo Clinic is the legendary place where
the President of the United States was treated.
Here, Chen Lieping can easily obtain oncology research samples
.
Thanks to this, he quickly found the answer
in the tumor microenvironment.
In 1999, Chen Lieping first reported the B7-H1 molecule (that is, the later famous PD-L1) in Nature Medicine, and proved that this molecule has immunosuppressive functions
.
In 2002, Chen Lieping was the first to report in Nature Medicine that PD-L1 is
produced in large quantities on the surface of a variety of cancer cells.
Interestingly, its production is mainly induced
by γ interferon.
Chen Lieping suddenly thought that T cells and tumors come into contact, release γ interferon, and activate the PD-1/L1 pathway, which induces local immunosuppression
.

In the abstract, he wrote prospectively: "These findings could lead to T-cell-based cancer immunotherapies
.
" Unfortunately, the scientific community has ignored Chen's view
.

03

The trough of tumor immunity

In the period when targeted therapy was in full swing, Chen Lieping silently did research and silently issued papers
.
"Whoever will eventually shake the world will be silent
for a long time.
"

He has delved into the physiological functions of PD-L1 molecules and has published a series of articles
.
He validated the safety of
the PD-L1 pathway as a drug target.
In 2005, Chen Lieping published results in Cell Research: in animal models, blocking the PD-L1 or PD-1 pathway with antibodies can improve the anti-tumor immune response and thus destroy tumors
.

This year, Chen Lieping was 48 years old, and his research laid a solid foundation
for the future research and development of "miracle drugs".
For more than ten years, he has explored alone, slowly merging the trickle into the great river and sea
.
At this time, Chen Lieping's heart was full of longing: "Inhibiting the PD-1/L1 pathway to awaken the immune system may be able to shine in the treatment of human cancer
.
" ”

"However, most people don't accept this new concept
very well.
" Chen recalls, "At that time, tumor immunologists used methods to enhance the immune response to fight cancer
.
They did not believe that the molecule PD-L1 would act selectively in
the tumor's microenvironment.
"After all, the tumor microenvironment is so complex and changeable, blocking the PD-1/L1 pathway with antibodies can clear the tumor, how is this possible?"

As early as the 50s of the 20th century, scientists discovered that the body's immune system was able to suppress the growth
of tumors.
A large number of lymphocytes are often present in tumors, and lymphocytes that kill cancer cells can be isolated from tumors (see section 20).

Puzzledly, lymphocytes in the tumor microenvironment are unable to stifle cancer growth
.
The cancer cells seem to say, "You hit yours, I'll grow mine
.
" ”

Conventional wisdom is that tumor growth and immune response are like a race
on the track.
If the immune response is weaker than the rate at which the tumor grows, then the tumor will continue to grow
.
If the immune response exceeds tumor growth, then the tumor is suppressed
.
Based on this assumption, the mainstream of tumor immunology is to enhance the immune response to fight cancer
.
In the past few decades, methods to "put the gas pedal" on the immune system include tumor vaccines, cytokines, cell therapies and oncolytic viruses
.
These methods raise the immune response to an intensity
above normal or not at normal levels.
However, these immune-boosting therapies have failed
in clinical trials for the treatment of solid tumors.
Especially at the beginning of the millennium, the failure of tumor vaccines led to a trough in
tumor immunotherapy.
Chen Lieping recalled: "At that time, many people thought that the immune system was useless in treating cancer, and many people also withdrew from this field
.
The group of us who stayed behind to study immunotherapy were diehards
.
”

Chen Lieping not only insists on it, but also holds a "non-mainstream" view: "The tumor microenvironment produces strong immunosuppression, no matter how you strengthen the immune system in other parts of the body, but the tumor site can still turn off the immune defense response
.
" His idea is: to localize the tumor microenvironment, through antibodies to release the "brakes" dragged by the tumor, so that T cells can run forward smoothly, thereby destroying cancer cells
.
However, the general environment of tumor immunity is at a trough, and the small environment of the Mayo Clinic is relatively conservative, and it is impossible for Chen Lieping to carry out human clinical trials
.

The wheel of the times is rolling forward, how can individuals open a new chapter?

04

A new chapter of the era

In 2004, Chen Lieping left Johns Hopkins University
.
Here, Chen Lieping meets another frustrated man
, Drew Pardoll.
Padol developed a tumor vaccine, hit a wall everywhere and entered a career low.

Chen has been telling Pador and Suzanne Topalian about the importance of
PD-1/L1.
Although oncology vaccines can induce a T-cell immune response, this response cannot be clinically effective
.
Why is this so? It is likely that the tumor creates a harsh microenvironment that inhibits the function of
T cells.

Suzanne has participated in clinical trials of CTLA-4 antibodies, which are the enhancement of systemic immune responses and lead to a high proportion of adverse reactions
.
Chen Lieping said to Susanni: "The immune system of tumor patients is different from that of normal people, but everyone has been ignoring this problem
.
The mechanism of PD-1/L1 antibody is different from any previous drug, neither directly targeting tumors nor simply regulating immune cells, but specifically targeting key immune escape mechanisms in the tumor microenvironment, and clearing tumors
by improving the tumor microenvironment.
In this way, the toxic side effects are
much smaller.
Suzanne agreed with Chan Lieping's point of view
.

At the time, Bristol-Myers Squibb was advancing clinical trials of CTLA-4 antibody drugs, but the superiority of PD-1 was clear
at a glance.
Therefore, Bristol-Myers Squibb began to attach importance to the concept
of Chen Lieping.
Chen Lieping's concept was that only localized treatment of the immune escape mechanism of the tumor microenvironment was safer and more effective, which was still relatively advanced at that time
.
Years later, it was proven that targeting PD-1/L1 was much better than CTLA-4, and the adverse reactions were much
smaller.
Back in 1997, Bristol-Myers Squibb switched to targeted therapy, missed Chen Lieping, and really missed the opportunity
to develop immunotherapy.
Bristol-Myers Squibb executives began to realize: "Immunotherapy is the future of
cancer treatment.
" "They immediately adjusted their strategy and reorganized the entire company to focus on oncology immunity
.
Putting all your eggs in the tumor immunity basket is definitely a brave gamble, risking everything and going
all out.
Bristol-Myers Squibb acquired the PD-1 antibody (nivolumab) through the acquisition of Medarui and re-established its connection
with Chen Lieping.

In 2006, it was a turning point
.
After more than two years of discussion and preparation, Chen Lieping and Suzanne cooperated to launch the world's first phase I clinical trial of PD-1 antibody, which is the famous O drug
in the future.
In 2006, a patient with advanced colon cancer in his 60s came to Johns Hopkins University Hospital
.
He tried chemoradiotherapy and targeted therapy, but failed
.
His intestinal tumors are large, and there are many metastases in his lungs
.
The patient was incurable and his condition progressed rapidly, so Chan's team chose to take the risk of implementing experimental therapy
.
New clinical trials are full of uncertainty, unknown efficacy, unknown risks, will it bring hope for life?

The doctor gave the patient a shot of PD-1 antibody
.
3 months later, during a full-body scan, his tumor was
completely gone.
Chen Lieping recalled: "At that time, almost no one believed this result, and everyone thought that the diagnosis was wrong
.
Doctors later re-examined him and found him completely cured
.
We also had a celebration
.
”

In order to promote clinical trials of PD-1 antibodies, Chen Lieping has been preparing for 10 years
.
Early clinical trials showed that some patients did regress tumors
.
But skeptics say the experiment is too small
.
In order to achieve a large-scale clinical trial with hundreds of patients participating in testing PD-1 antibodies, it took 6 years
for Chen Lieping.
The data he obtained on tumor regression once again shocked
everyone.
In some patients, the cancer disappears completely and no longer recurs
.
Chen Lieping was excited: "People are starting to believe that this is true
.
”

In 2012, the results of the first clinical trial of PD-1 antibodies were published
in the New England Journal of Medicine.
Patients with metastatic melanoma, colorectal cancer, non-small cell lung cancer, prostate cancer, or kidney cancer who have failed multiple lines of therapy are all effective
after PD-1 antibody therapy.
Chen Lieping's 15 years of hard work have finally translated into visible results
.

Immunotherapy has three characteristics: first, accessibility, which can treat patients with widely metastatic and "untreatable" advanced cancer; Second, it has a broad spectrum and can treat a variety of different cancers; Third, it is durable, because the immune system has a memory function, once immunotherapy takes effect, some patients can achieve clinical cure (no recurrence or metastasis after 5 years of treatment).

"Ten years of drinking ice, it is difficult to cool the blood
.
" Since then, mankind has entered an epoch-making new chapter
in immunotherapy.

05

It's sad to miss the Nobel Prize for half a minute

When Chen Lieping succeeded in a foreign country, he often remembered the scene
of his own work in the domestic oncology department in the 80s of the 20th century.
At the same time, he had the idea of returning to China: "I want to make immunotherapy
available to patients in China as soon as possible.
" ”

In 2006, when Chen Lieping initiated the first clinical trial of PD-1 antibodies in the United States, the Chinese pharmaceutical industry was undergoing changes
.
From 2000 to 2006, China's generic drugs developed rapidly, and China's drug approval entered a "period of expansion", and a large number of generic drugs were approved
.
At this time, the domestic enthusiasm for small molecule targeted drugs has even reached a certain level of
madness.

In 2008, definitive progress
was made in the Phase I clinical trial of PD-1 antibodies.
Chen Lieping flew back to China, he wanted to take the lead in opening the era of tumor immunotherapy in China, but he was coldly received
.
Chen Lieping is also helpless, in the field of tumor immunotherapy, China has missed the development opportunity
.
Since then, he has been looking for opportunities to return to China
.
Until 2012, the phase I/II clinical trial of the anti-PD-1 drug ended, and the results were promising
.
Chen Lieping spent a lot of time preparing application materials and intending to apply for the transformation of
major scientific research projects.
But the judges did not recognize the importance of the work, and Chen Lieping failed again
.

Chen Lieping returned to his hometown disappointed, to Fujian Medical University, where his mother was a professor
.
In 2013, Chen Lieping received support from his alma mater, Fujian Medical University, which led to the establishment of a laboratory
in China.
The teacher of his alma mater said to Chen Lieping with a smile: "You have won the sports championship in Fujian Province many times before, and we all think that you are the seedling of athletes
.
Unexpectedly, you have overcome difficulties on the road of scientific research and become a scientist
.
”

Chen Lieping also did not expect that when he established a domestic laboratory, the first opportunity was lost
.
It was this year that immunotherapy was named the most important scientific breakthrough
of the year.
In 2014, PD-1 antibodies were approved for marketing
in the United States.
Subsequently, PD-1/L1 antibodies have found breakthroughs in more than 10 cancers such as melanoma, non-small cell lung cancer, and head and neck tumors, and gradually become first-line treatment drugs (see Appendix I).

It wasn't until June 2018 that immunotherapy began in China, when Chinese patients finally became available (see section XVIII).

The American scientific community is also seniority
.
Compared with many "academic superstars", Chen Lieping belongs to "no sect and no sect"
.
In this case, Chen Lieping worked hard all the way for 20 years
with perseverance.
Its PD-1/L1 research work spans basic research, translational research to clinical practice, and has brought benefits
to countless cancer patients.
While Allison and Honjo vigorously promote their work around the world, Chen Lieping still explores
quietly, diligently, and alone.

Will he be judged fairly?

On August 1, 2014, Chen Lieping won the William Coley Award
, the top award in tumor immunology.
What's more, on June 7, 2017, Chen Lieping won the Warren Alpert Award
.
Only scientists who have made outstanding contributions to the prevention, treatment and development of human diseases and to the field of human understanding of diseases are eligible for this award
.
Among the previous Alpert Prize winners, many have also won Nobel Prizes, including Tu Youyou
.
In 1969, Tu Youyou was ordered to lead the team to overcome many difficulties and discover artemisinin, saving millions of lives
around the world under the condition of backward equipment and difficult environment.
In 2015, Tu Youyou became China's first Nobel Prize winner in physiology or medicine
.
At this time, the Chinese public discovered such a little-known "three no" scientist (no doctorate, overseas background and academician title).

This is the star
we are chasing.

Before October 2018, Chen Lieping was once seen as a potential Nobel Prize winning scientist
.
When the winners of the 2018 Nobel Prize were announced, he was not among them
.
This stirred up a wave of public opinion, and many people expressed regret: "This is the hidden discrimination and unfair treatment
suffered by Chinese scientists.
" But Chen Lieping responded in a media interview: "I used to feel a little sad, but I was sad for 30 seconds, and I was not sad after a minute
.
" ”

In his opinion, PD-1/L1 belongs to the past
.
Today, his job is to address the problem
that 80% of patients do not respond to PD-1/L1 antibody therapy.
Regarding Allison's immune checkpoint theory, Chen Lieping believes that this theory will be misleading
to the drug development of immunotherapy.
Can suppressive immune molecules be used as "immune checkpoints" to treat tumors? In 2018, immunologist Liu Yang found that the immune checkpoint hypothesis of CTLA-4 antibodies (ipilimumab) in immunotherapy does not hold
.
Ipilimumab does not exert anticancer effects by blocking the CTLA-4/B7 interaction, but rather by clearing locally regulatory T cells of the tumor
.

This instead hints at the importance of
reshaping the tumor microenvironment.

06

Turbidity and clarity

Chen Lieping's efforts for more than 20 years have witnessed the transformation of tumor treatment ideas: from the era of tumor molecular biology to the era
of tumor microenvironment.
One step at a time, everyone can be a part of
this great era.

Today, in the field of oncology, modifying the tumor microenvironment is the key to
overcoming cancer.
We can adopt two strategies to achieve the goal: (1) shift the focus of treatment from the attack on the cancer cells themselves to destroying the microenvironment that maintains tumor growth and survival; (2) Improve the immune microenvironment and fully mobilize the immune system so that it can eliminate cancer cells
like an infection.
Reshaping the environment, stirring up the clear, has great
potential.
For example, in 2020, Li Ming of MSK Cancer Center proposed "environmental immunotherapy for cancer"
.
Compared with activating the immune system to fight cancer cells "head-on", by activating the immune system to reshape the tumor microenvironment and prune the blood vessels that nourish cancer cells, cancer cells can also die
due to lack of oxygen in a "roundabout" way.

The interaction between the tumor microenvironment and the immune system is indeed very complex, how to benefit more patients? Chen Lieping does not forget his original intention and keeps moving
forward.
Today, he moves to Yale University as director
of immunology at the Cancer Center.
No matter how his identity changes, his interests have not changed, and he has always focused on cancer immunotherapy
.
He now has many roles, engaged in basic research in the laboratory, opened a company to do translational research, and carried out clinical research
in the hospital.
Chen Lieping admitted: "Doing research, doing business, and doing clinical practice requires understanding three different languages, and it is not easy to
do this.
"At present, based on the findings of Chen Lieping's laboratory, in addition to PD-1/L1 antibodies, multiple drug candidates (LAG-3, S15 and other antibodies) have entered clinical trials and achieved positive results, which is expected to provide new hope
for PD-1 resistant patients.

"If I only focused on basic science, I would probably publish twice as many articles
as I do now.
" Today, for Chen Lieping, publishing articles is no longer the most important thing
.
After all, treating and saving people is the original intention, and the original intention that was born when he entered the oncology department in 1982 at the age of 25 has never changed
.

Many pharmaceutical companies believe that cancer can become a chronic disease
.
But Chan's vision is: "We want to cure tumors, not take drugs
for life.
" ”

The reason why Chen Lieping took it personally, spending time and effort to do clinical and enterprise, the original intention is to develop curative drugs
through his own efforts.
In this sense, we can better understand why Chen Lieping calls himself a "lone explorer"
.
For 20 years, not recognized by mainstream academics, he explored
alone.
Now, as everyone rushes into the PD-1 track, he's retreating to explore other immune escape pathways
alone.

Approaching Chen Lieping's world, you can feel that the most primitive things in life are actually not in the noisiest place in the world, nor in the most glorious moment
.

As soon as he had time, Chen Lieping flew back to China, to his hometown, to the place where his dream began, to lectures, to give lectures, to discuss.
.
.
In the 10 years when tumor immunity was at a low point, Chen Lieping's lectures often had only one or twenty listeners
.
Now Chen Lieping's speech is empty
.
On June 29, 2019, the heat wave in Tianjin was rolling, and the China Conference on Immuno-Oncology was held
here.
Chen Lieping wore black-framed glasses and his eyes were like torches, and he spoke from the pulpit
.

"The immune system is finely and subtly regulated, and boosting immunity is a dangerous practice
.
I'll use a water pipe as an example
.
The immune response under normal conditions is like the normal flow
of water.
Once there is a blockage in the middle of the water pipe, the flow of water cannot pass
.
The place of blockage is like the location of the
tumor.
One of the solutions is to increase the water pressure and force the flow of water through (immune booster); Another way is to find the site of the defect and selectively remove the obstruction to allow water to flow through (immune normalization).

Anti-PD therapy uses the latter approach: finding pathways that suppress immune responses in the tumor microenvironment, then blocking that pathway to
normalize the immune response.
Therefore, I recently proposed the concept of immune normalization, which adjusts the deteriorating tumor microenvironment to a normal state, thereby treating cancer
.
”

The theory of "immune normalization" provides a completely new framework for cancer immunotherapy, which is far-reaching
.
Chen Lieping came from the Chinese school and put forward theories that shimmer with the wisdom
of Chinese culture.
An old Chinese saying: "Evil cannot be done
in the midst of righteousness.
" "Within the tumor microenvironment, there are too many evil accomplices
.

"Turbidity and clarity, dispelling evil and helping the righteous" is the right way
to treat tumors.