Natural Killer Cell therapy in China

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March 2024: The number one enemy of the world ’s medical community is tumors. Speaking of cancer, it can be said that cancer causes discoloration, and a scientist in China has developed a new method of treating tumors. From its own cells, I have found a strong enemy against cancer.

Zhang Minghui of the Cell Therapy Research Institute of Tsinghua University Medical Center is the person in charge of this project. He and the team’s job is to find and cultivate immune cells that are beneficial to human health from the numerous cells in the human body.

Keeping immune cells is not as simple as keeping pets. The fine extraction of immune cells is very difficult. It needs to be identified and sorted out one by one with professional equipment. The growth requirements of cells in vitro are more demanding, and they need to grow up under special conditions such as constant temperature, constant humidity, and constant carbon dioxide concentration. They are also particularly picky eaters, and different cells have to eat different nutrients. Ordinary nutrients are insignificant. And finding and cultivating rare immune cells is like finding a needle in a haystack.

In 2005, Zhang Minghui ’s students accidentally cultivated an immune cell. The size of this cell was seven or eight times larger than that of other cells. Zhang Minghui judged the special function of this “big” cell based on years of professional sensitivity. His team left this cell and conducted a systematic study of it. They were pleasantly surprised to find that they found a subpopulation of NKT cells, which is a super killer in the immune system and can actually kill cancer cells.

The so-called NKT cells were first named by Japanese scholars more than 20 years ago. NKT is the abbreviation of “natural killer T cell” in English. The main function of this cell is to release danger signals to other immune cells.

The world’s progress in cancer immunotherapy can be traced back to the late 1980s, with research in the United States and Japan at the international frontier. In 2013, the famous “Science” magazine ranked immune cell therapy among the top ten scientific and technological advances of the year. China has always lacked innovative discoveries in this area.

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The team of Zhang Minghui discovered the research results of the new subpopulation of NKT cells, and it immediately attracted international attention after it was published in a scientific report in the journal Nature in 2015.

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Zhang Minghui named them CD8 + NKT subgroup. With the help of a high-power microscope, we saw the whole process of this subgroup fighting against cancer cells. In more than two hours of confrontation, this group of NKT subpopulations wiped out a group of highly malignant cancer cells.

It is one thing to kill cancer cells in an experimental environment. Can they play the same role in the human body?

Since 2010, Zhang Minghui has cooperated with the First Affiliated Hospital of Tsinghua University to recruit volunteers for clinical trials. Zhang Minghui will come every month to analyze the effect with the doctor.

Yang Guoshan, chief physician. Usually, the treatment of a tumor is to remove the lesion, and then use adjuvant therapy such as chemotherapy or radiotherapy. Yang Guoshan often encountered tumor resection surgery. In his view, tumor surgery is only a partial cleanup, that is, the visible cancer cells are cleaned up, and the grass surgery that can be seen clearly is just like pulling the grass, but it cannot be Explain that this land will not grow grass, but it will definitely grow, so what should I do? You can only spread medicine. Chemotherapy is like spreading medicine, and those that are going to grow up or that are not long will be eliminated in the future.

Although chemotherapy can kill cancer cells that cannot be cut off, it can also kill normal cells, and the treatment process is extremely painful. The pain that chemotherapy causes is unbearable for many patients. Even if it can be tolerated, it is difficult to kill 100% of the cancer cells. In theory, as long as a seed is left, it may have the possibility of making a comeback. At present, traditional surgical radiotherapy and chemotherapy can solve this problem well if symptomatic, but once there is a risk of distant metastasis and recurrence, once it gets up, then our traditional methods are helpless.

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Cellular immunotherapy technology is called the fourth tumor treatment method after surgery, radiotherapy, and chemotherapy. Zhang Minghui believes that NKT subpopulation cells are present in everyone’s immune system, but the content in each person’s body may be different, which is why in the same environment, some people tend to grow tumors, while others are easy to grow tumors. Cancer patients usually have few autoimmune cells. Zhang Minghui began to extract and culture the blood of their immediate family members.

The NKT subpopulation cells in normal human body are also very few and difficult to find. They collected the seeds of NKT subpopulation cells from the human body, sent them to a very low temperature environment for training, and then waited for the first round of selection in the Petri dish.

There, Zhang Minghui and his team will increase their numbers by special means and stimulate training, which is a key link to equipping cells with weapons and ammunition. It is not difficult for cell culture masters to expand their strength, but the difficulty is to ensure that each of them is a strong soldier.

This team has now mastered the secret of training. They can expand the NKT subpopulation cells from one to thousands in more than half a month, and all of them have worked hard.

How do these “special forces” enter the patient’s body? The image they are analyzing today comes from a patient with stage III gastric cancer. This patient had a third of his stomach removed in 2011 because he was so painful that he insisted on completing two courses of chemotherapy. Eight months later, the tumor metastasized to the lungs.

After the discovery of the transfer, the patient applied to become a volunteer for immunotherapy. The information has now lasted for more than three years. According to past experience, once gastric cancer has metastasized to the lungs, the patient’s life is only about half a year. Medical imaging data shows that after more than three years of treatment, the patient’s symptoms have been significantly relieved, and the doctors are also very excited.

But different human bodies are very different. Whether this cell immunotherapy can be effective for more cancer patients is still very cautious. Only by accumulating enough cases can the problem be explained. In the past five years, they have recruited more than 70 volunteers. Among the 30 patients who have been treated for more than one year, about 70% have shown a significant improvement.

There are many patients who want to be volunteers. Now, Zhang Minghui takes one day a week for consultation. Clinical trials require a very scientific and cautious attitude. From the current research, this NKT subpopulation cell is not a panacea, it also has its own weaknesses. There are immune barriers in the brain, glands and other places of the human body, and the cells cannot enter. For these tumors, the effect is weaker.

Because of the originality and advanced nature of immune cell technology, the project of the Zhang Minghui team won special support from the National Twelfth Five-Year Fund in 2010.

Now, the safety and effectiveness of the clinical phase 1 trials have initially appeared, and Zhang Minghui has begun preparing for large-scale clinical research this year.0


Dr. Zhang Minghui


Zhang Minghui, Doctor of Immunology, Associate Researcher, and Supervisor of Master Students; Director of the Cell Therapy Research Institute of Tsinghua University Medical Center; Deputy Chairman of Tsinghua University Committee of Jiu San Society. Recipient of 100 excellent doctoral dissertations nationwide in 2005, and expert in new drug review by CFDA New Drug Review Center.

It is the first in the world to establish a large-scale expansion method of NKT, discover the two-way anti-tumor effect of NKT, and create a new generation of anti-tumor immune cell therapy technology based on NKT. The Ministry of Health’s “Twelfth Five-Year” major new drug creation plan provided funding for “the new generation of anti-tumor immune cell therapy technology based on NKT” and it entered clinical research.

He won the top ten scientific and technological progress awards of national colleges and universities in 2004, the first prize of the 2006 Chinese Medical Science and Technology Award, the first prize of the 2006 Shanghai Medical Science and Technology Award, and the 2009 mentor and friend award of Tsinghua University. I presided over many national projects, such as the Natural Science Foundation, major new drug creation plans, major infectious disease plans, and the “863” plan.

How do NKT sub-population cells fight cancer cells, and what breakthroughs does China have in the field of biotechnology, CCTV Financial Channel 21:50, Saturday, February 27, “China Financial Report,”  see “Feeling China’s New Kinetic Energy: Immune Cell Counter Cancer.”.

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