Shen Baiyong from Ruijin Hospital: Sound the alarm before the pancreatic cancer alarm goes off

Pancreatic cancer is known as the "king of cancer" because it has no obvious clinical symptoms in the early stages and is mostly discovered in the late stages.

At the 25th Shanghai International Biotechnology and Pharmaceutical Symposium on Clinical Demand-Driven Innovative Drug Development, Shen Baiyong, Vice President of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, introduced that the one-year survival rate of pancreatic cancer patients worldwide is more than 20%, and the five-year survival rate is 7%-10%. "If I can extend the life of patients, or even keep them alive, that would be a wonderful thing," Shen Baiyong said.

This self-expectation has given him an inexhaustible motivation to develop innovative drugs. Shen Baiyong's team has reached the world's leading level in the field of pancreatic cancer treatment. Its T cell receptor T cell therapy (TCR-T) clinical trial for advanced patients has officially started. This is China's first new study on pancreatic cancer immunotherapy, which will open up a new treatment path for patients. Shen Baiyong said, "We will definitely be able to make the best pancreatic cancer cell treatment in the world, and I believe this is just around the corner."

Conquering pancreatic cancer: shifting from immunotherapy to cell therapy

Faced with pancreatic cancer, the "king of cancer", humans seem to be somewhat helpless.

T lymphocytes are the main force of the immune system against cancer. The human immune system can recognize and kill cancer cells, but cancer cells can sometimes escape the attack of the immune system. This is because cancer cells use immune checkpoints to inhibit the activity of T lymphocytes, thereby weakening the immune system's defense against tumors. Conversely, blocking immune checkpoints can reactivate T cells and help the immune system eliminate cancer cells.

Among the many immune checkpoints, PD-1 is an important target, which is widely used in immunotherapy and shows good effects in the treatment of various cancers.

However, this immunotherapy method has little effect on pancreatic cancer. Shen Baiyong's team found that PD-1 has some pancreatic cancer patients who are suitable, such as those with high tumor mutation load and microsatellite instability, but the overall effect is not satisfactory. "The targeted drug therapy such as PD-1 that everyone is familiar with is not effective in the treatment of pancreatic cancer, so we will turn our attention to cell therapy." Shen Baiyong said.

"We turned to T cells with 'missile' functions, which can recognize cancer cells and carry out specialized attacks, which is the biggest difference between it and PD-1."

Compared with targeted drug therapies such as PD-1, the cell therapy technology developed by Shen Baiyong's team has made significant breakthroughs. "We use the patient's own T cell receptors to identify tumors and kill and eliminate them. We use genetic engineering methods to separate T cell receptors that recognize tumors, and load these T cell receptors onto the patient's own T lymphocytes in vitro to prepare TCR-T cells, which can enable the patient's own T lymphocytes to acquire the ability to recognize and kill their own tumors." Shen Baiyong said, "In the treatment of pancreatic cancer, we have successfully entered the clinic with this technology, and the current results are very ideal."

There are both advantages and disadvantages. Shen Boyong admitted that the current T cell therapy is not suitable for all pancreatic cancer patients. "PD-1 is a universal treatment method. The current prerequisite for using T cell therapy is that the patient meets the two subtypes of KRAS or/and TP53 gene mutations we developed." He introduced that currently, patients who meet the matching conditions account for about 10% of the total number of pancreatic cancer patients. "We are constantly developing new mutation points. As the range of subtypes expands, the proportion of patients who can be treated will increase. I believe that in the future TCR-T will be able to cover most of the mutation subtypes of pancreatic cancer." Shen Boyong is full of confidence.

From basic to clinical: What can we do?

"We need to answer some major scientific questions in theory, such as the molecular classification of pancreatic cancer, why cancer occurs, and how cancer cells grow." Shen Baiyong has high expectations for basic research. At the same time, as a clinician, he also hopes to break through the current bottleneck of treatment.

A major bottleneck in the treatment of pancreatic cancer is the low rate of early diagnosis. Shen Baiyong said that the early diagnosis rate of pancreatic cancer is only 20%, and most pancreatic cancer patients are already in the middle or late stage when diagnosed. However, there is a significant difference in the five-year survival rate between early pancreatic cancer patients and late stage patients. Faced with such a dangerous "cancer king", early diagnosis is crucial to the overall treatment of pancreatic cancer.

Shen Baiyong introduced that there are usually two diagnostic criteria for pancreatic cancer: one is imaging examination, including CT, MRI, PET-CT, etc.; the other is to check the increase of tumor indicator CA19-9. CA19-9 is a tumor biomarker, and the determination of CA19-9 in serum is widely used in the differential diagnosis and disease monitoring of pancreatic cancer. In the serum of healthy individuals, the concentration of CA19-9 is low, but when there is a malignant tumor such as pancreatic cancer, the concentration of CA19-9 will increase.

However, these traditional methods of testing fall behind the "alarm" of pancreatic cancer. According to the former, the tumor that can be seen by imaging is "already very large"; according to the latter, "if the CA19-9 level is higher than 100U/ml, it is basically pancreatic cancer."

Shen Baiyong and his team tried to outrun the "cancer king" and "sound the alarm" before the "alarm" sounded. Through self-developed test kits, they tried to detect cancer earlier than tumor indicators. "As long as there are cancer cells, there will be traces in theory. The trace we have caught is cfDNA methylation." The free DNA in the blood is referred to as cfDNA (circulating free DNA), which refers to nucleic acid substances in circulating blood. cfDNA exists in various body fluids of the human body, and its concentration changes with tissue damage, cancer, and inflammatory response. The cfDNA molecules produced in the body will be rapidly degraded, with a half-life of less than 1 hour or less. The concentration of cfDNA in peripheral blood (that is, blood other than bone marrow, which has been released into the circulatory system by hematopoietic organs to participate in circulation) is mostly less than 100 ng/ml, with an average value of about 30 ng/ml. In tumor patients, the concentration of cfDNA in peripheral blood can be as high as 1000 ng/ml, with an average value of about 180 ng/ml.

"By using a test kit to detect the concentration of cancer cells in the peripheral blood, we can detect pancreatic cancer 3 to 6 months before CA19-9 rises," said Shen Baiyong.

"Managing the high-risk population for pancreatic cancer is very beneficial for the early diagnosis of pancreatic cancer as a whole," said Shen Baiyong. "Every year, 3,000 to 4,000 pancreatic patients come to our pancreatic center for treatment. We have the mission and responsibility to improve the early diagnosis and treatment of pancreatic cancer based on clinical needs."

“China’s innovative drugs are about to emerge”

China has made remarkable progress in pancreatic cancer treatment worldwide, becoming a "global leader on par with the United States." At the 25th Shanghai International Biotechnology and Pharmaceutical Symposium on Clinical Need-Driven Innovative Drug Development, Shen Boyong said that the factors for success are multifaceted.

“First of all, the level of China’s overall research infrastructure is already on par with the best in the world.” He went on to analyze the research atmosphere in our country.

"The Chinese government strongly supports innovation-driven development, from laws and regulations to policy support, to encourage scientists to conduct innovative research... In a word, the state has completely relaxed the patent protection and patent conversion (further standardization) for medical researchers, and I am an eyewitness."

In Shen Baiyong's view, this favorable environment is an important condition for his team to achieve the current results. In addition, China has a large population and has accumulated a large number of samples, which provides valuable resources for clinical research. Compared with other countries, China can have more patients, providing a broader platform for the research and practice of pancreatic cancer treatment.

Roundtable discussion on "Translational Medicine Achievements and Biopharmaceutical Industry Development"

At the roundtable discussion on "Translational Medicine Achievements and the Development of the Biopharmaceutical Industry" at the seminar, Shen Baiyong called on "I hope that all sectors of society can pay attention to innovative drugs, including financial support, which is very important for the entire research and development of new drugs. Because the significance is not only in how much sales returns can be generated, but also in solving some problems in the entire disease field."

“I think China’s innovative drugs are about to emerge.

In the field of pancreatic cancer cell treatment,

We are currently competing in the first tier of the world.

We will certainly be able to

The best pancreatic cancer treatment in the world,

I believe it is just around the corner.”

Shen Bai said with a firm look.