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An interview with Dong Chen, Professor of Tsinghua University

time:09/21/2017 page views: resource:BioBAY

By the year 2017, Professor Dong Chen has insisted on immunology research for 27 years. In nearly thirty years of his research career, he published about 200 papers in Nature, Science and other magazines, and was elected by Thomson Reuters as "Highly Cited Scientists" for three consecutive years. He has made many pioneering contributions in the field of T cell differentiation and autoimmune diseases and is one of the founders of Th17 cells and Tfh cells. He founded "Suzhou Xin Kang He Biomedical Technology Co., Ltd." in BioBAY in 2015 and transformed his research achievements into innovative and best-in-class antibody drugs for cancer and autoimmune diseases. Today, I will bring you closer to the famous immunologist - Professor Dong Chen, Dean of Tsinghua University School of Medicine.

Professor Dong Chen (Source of the picture: network)

In July of this year, Professor Dong Chen, director of the Institute for Immunology, Tsinghua University (IITU), published an article online entitled "Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function" in Cell Research. The study revealed the negative regulatory role of B7-H3 immune checkpoint in the anti-tumor immune response and confirmed that the combination of B7-H3 antibody and PD-1 antibody is expected to further improve the latter's efficacy, especially for advanced tumors. 

It is reported that the research group has worked on B7-H3 molecule for many years, and at the early age was mainly concerned about its role in autoimmune diseases and immune tolerance. With more and more studies showing that the molecule involved in immune tolerance is more or less used by tumors to fight the immune system, the team began to investigate the role of B7-H3 in tumor immunity. The research found B7-H3 is highly expressed in the tumor microenvironment, thus blocking this molecule can effectively inhibit tumor growth.

In the biodiscover interview, Professor Dong Chen revealed that, the research group will carry out further research in two aspects next: first of all, in the basic research, they hope to have a deeper understanding of the functions of B7-H3 (such as regulation of T cells and NK cells) and downstream molecules of action, regarding B7-H3 as a starting point to find more on the regulation of tumor immunity molecules and pathways; then, the research team hopes to be able to investigate the expression and function of B7-H3 in other types of cancers (previously mainly in melanoma and liver cancer) in combination with clinical specimens. Professor Dong Chen stressed the differences with B7-H3 and its regulatory pathways and PD-1/ PD-L1 pathways need to be studied on the human samples.

1. Hot: ancer immunotherapy

In recent years, the rapid development of cancer immunotherapy has become one of the hottest research directions in the field of biomedicine. Professor Dong Chen told biodiscover, the laboratory personnel are also fully committed to cancer immunotherapy, the main directions include: 1) to further explore the role of immune tolerance molecules involved in tumor immunity; 2) to investigate how the killer T cells is regulated in the tumor microenvironment; 3) to focus on the inflammatory reaction associated with tumor development.

He said: “As for the second point, after clarifying the regulatory mechanism of killer T cells, we can enhance its anti-cancer effect through the regulation of such cells; And as for the third point, after figuring out how inflammation promotes tumorigenesis, we can reduce these cancer-promoting inflammatory responses as an anti-cancer strategy. The combination of ‘enhancing anti-cancer effect’ and ‘inhibiting cancer-promoting effect’ may lead to better cancer treatments.”

In fact, the current cancer immunotherapy is really not enough to save the lives of a wider range of cancer patients. Even the most successful immune checkpoint inhibitors (such as PD-1 / PD-L1 antibody), only a small number of patients can benefit from this therapy. This situation is now a big difficulty faced by immunology and the pharmaceutical industry.

Professor Dong Chen believes that in addition to the combination with chemotherapy and radiotherapy, the combination of inhibitors at different immunological checkpoints is another important branch. However, it is noteworthy that the effect of this combination of treatment in different cancers is very different. For example, the combination of PD-1 and CTLA-4 antibodies has been proved to work well in the treatment of melanoma, but its efficacy in the treatment of lung cancer is less than satisfactory. Therefore, tumor is not a common disease. In the future, in addition to combination therapy, personalized treatment also needs to be considered.

2. Immunology: he has been working in the field of immunology for 27 years.

Since his studying for a doctor's degree in 1990, Professor Dong Chen has been working in the field of immunology for 27 years. He told biodiscover that many diseases have been conquered with the development of immunology, including autoimmune diseases and cancers. Looking back on past 27 years, Professor Dong Chen said humorously: “Men should choose the right career, just as women should choose the right husband. Luckily, my initial choice is right.”

In fact, during the past 30 years, Professor Dong Chen has made a great deal of important research results. He has published about 200 papers in Nature, Science and other magazines and the total number of citations is more than 20000. In 2014, 2015 and 2016, he was selected as “Highly Cited Scientist” by Thomson Reuters continuously. He has made many pioneering contributions in the field of T cell differentiation and autoimmune diseases and is one of the founders of Th17 cells and Tfh cells (follicular helper T cells).

Professor Dong Chen recalled: “In recent years, I have done much work in the field of follicular helper T cells (Th). I started studying Th cells in 1997 when these cells included both Th1 and Th2 subsets. After 20 years of development, there are currently two new subpopulations of Th cells, Th17 and Tfh. The discovery of these two types of cells are closely related to our work. The most comforting thing is that Th17-related basic research has quickly been transformed into the patient's available antibody drugs. ”

It is understood that in 2005, Professor Dong Chen’s laboratory and two other laboratories almost simultaneously found Th17, a new T-cell subpopulation. This is a class of T cells that secrete interleukin 17 (IL-17), which is closely linked to inflammatory diseases, including autoimmune diseases. This finding has prompted pharmaceutical companies to develop IL-17 related antagonistic antibodies. In 2015, the first IL-17 antibody Cosentyx was approved of going public. At present, such antibodies have been approved for the treatment of psoriasis, arthritis and ankylosing spondylitis.

During the interview, he talked about the transformation of basic research and shared with biodiscover the reason behind the low transformation rate of domestic scientific research achievements. He concluded: “This is mainly related to three factors: First, the transformation of scientific research achievements does require a relatively strong level of basic research which is weak in domestic research before. However, it is gratifying to note that in the near future, the volume of basic research in China has been gradually increasing, and its originality has also been on the rise. Second, at present, the overwhelming majority of researchers in China carry out research based on some issues of their own interest. But in fact, some scholars need to pay attention to and study human diseases; Third, the transformation of basic research into industrial products lacks an important "bridge" link in China. Besides, turning the concept of basic research into an "initial product" through this process will be more conducive to the actual application by pharmaceutical companies. ”

3.He came to Tsinghua University to make contributions to the society and people.

Up to now, Professor Dong Chen, Dean of Tsinghua University School of Medicine, has returned to China for more than five years. In 2012, he began to set up institute for immunology at Tsinghua University. At the time, he was a lifelong professor and director of the Center for Inflammation and Oncology at the MD Anderson Cancer Center at the University of Texas.

When talking about why he decided to go back to China and set up an institute for immunology at Tsinghua University, Professor Dong Chen said: “Immunology is closely related to human health and disease treatment, and our country lags behind in its development in this area. I hope that by establishing a strong research team on immunology, we will make progress and breakthroughs in basic research and eventually push forward the development of new drugs for the benefit of the community.”

It is known that, after the development of the past five years, Institute for Immunology, Tsinghua University (IITU) already has 14 PI, whose research fields covering all aspects of immunology, including allergies, autoimmune, tumor immunity, etc.

In the interview, Professor Dong Chen told biodiscover there are two urgent problems to be solved in the field of immunology. First, although scientists are more aware of CD4 T cells, CD8 T cells and other natural lymphocytes, it remains unclear how these immune cells interact with each other. Current research is more concerned about a single type of cell, while ignoring the association and interaction between different types of immune cells. Second, in fact, the development of immunology in these years is more based on the mouse model. Affected by the strains and growth environments, the complexity and diversity of the immune system are not fully demonstrated. By now, the research on human immune system is not enough. Professor Dong Chen said, in the future, he hopes to try to explore the laws in this field of research and development, thus providing more clues for scientists who have joined the research of human immune system.

4. Doing scientific research should focus on one direction.

At the end of the interview, Professor Dong Chen emphasized: "Although, most of the time, doing scientific research is boring and there is always more "negative results" than "positive results", but scientific research itself is a very valuable thing. This sense of well-being will become even more pronounced when you discover some previously unknown laws and solve problems you have not previously solved.”

He added: “For doing research, it is better to focus on one direction and then do it systematically. I often tell my students that all you have to do is to solve a problem at your best. The discovery of most major achievements requires a process of accumulation. When you persevere and finally produce groundbreaking results, the significance of doing scientific research will be truly reflected.”