Promoting public health through immunological advances

Increasingly diagnosed throughout the world, primary immunodeficiency diseases (PID) are a group of rare genetic disorders triggered by the life-threatening failure of immune system in early childhood. With 30 years’ of experience, and leading a team of paediatric immunologists at the Shanghai Children’s Medical Centre, Tongxin Chen, president of the Shanghai Society for Immunology (SSI), targets the complexity of PID’s 400 subtypes, and further enables PID classification using only blood samples. By analysing and comparing a large number of clinical results, he combines genomic analysis and immunophenotyping to facilitate precision treatment. This integrated technique has since transformed the study of other complex diseases.

His findings, among others by SSI members, have been published extensively in leading international journals, including papers on diversity in the immune system, function of immune cells, epigenetic regulation of immune cells, metabolism, and inflammation-related diseases. As the earliest professional non-profit academic organization dedicated to immunology in China, SSI has promoted basic, translational, and clinical investigations since 1979. It is also the first in China to publish, in 1981, a professional publication dedicated to immunology, Current Immunology.

Driven by the founding mission of the pursuit of scientific truth, and the synergy of education and research, SSI is recognized for promoting the practice and development of translational medicine, interdisciplinary integration, and the collaboration between immunological and clinical experts. SSI has been leading collaborative efforts among the Shanghai Institute of Biochemistry and Cell Biology, CAS, and the Second Military Medical University and its National Key Laboratory of Medical Immunology (NKLMI).

Accelerating targeted therapies

A major area where precision medicine and immunological studies overlap is in the exploration of immunotherapies.

Xuetao Cao, a member of the Chinese Academy of Engineering, and a founding director of the NKLMI, has been studying dendritic cells (DC), which are immune cells that mediate cellular immune responses by processing and presenting antigens to activate natural killer cells, and have a critical role at the interface between the innate and adaptive arms of the immune system. DC-based immunotherapy is considered safe and promotes anti-tumour immune responses, prolonging the survival of cancer patients.

The team led by Yiwei Chu from Shanghai Medical College of Fudan University has outlined a ‘Fast DC’ strategy. It is a speedy protocol for the generation of DCs in vitro, which saves time and increases efficiency during the preparation of DC-based therapeutic vaccines, and adoptive cell transfer therapy. In addition, Chu’s immunotherapies based on CAR-T and Bi-specific T-cell engagers (BiTEs) have also undergone clinical studies with international partners, and been awarded patents.

At Shanghai Ruijin Hospital, a research team led by Xianghui Wang focuses on reducing the side effects for organ transplant recipients. The immune system attacks anything foreign to the body. In the context of organ transplant, such immune rejection can be fatal. Drawing on transplant experiences, Wang and his team have developed new personalized strategies to fine-tune the cocktails of immunosuppression drugs, keeping the necessary immune functions with minimized impact during kidney transplants.

Enabling breakthroughs with genomics

Attacks on the healthy tissues by the immune system through a systemic damage of organs and tissues can also be launched by autoimmune diseases, such as lupus. One research direction is through genomics.

Nan Shen, director of Shanghai Rheumatism Research Institute, has led a team in uncovering the genetic cues underlying Systemic Lupus Erythematosus, the most common form of lupus. With genomic analysis, Shen and his team identified a fragment of genetic material, named micro-RNA146a, which plays an important role in activating a gene associated with lupus. In 2019, Shen and colleagues published in Cell the discovery of a new mechanism, by which the degradation of circular-RNA molecules contributes to lupus through the regulation of innate immunity. This bridges the disease mechanism of lupus with innate immunity, and provides a molecular basis for new diagnosis and clinical therapy.

Naishuo Zhu, a microbiologist at the Fudan University School of Life Sciences, is studying new vaccines with genetic engineering technologies. His team has uncovered a series of functional elements of immune proteins, which can be cloned into a vaccine against various pathogens. Compared with conventional vaccine strategies, this new technology is more specific to target tricky pathogens, such as influenza, hepatitis B virus, or tumour cells, which are hard to kill via a general immune reaction using previous vaccines. These studies are promising for effective therapeutic options, and some are being tested by clinical trials. Zhu and colleagues, including Zhiyong Ma from Shanghai Veterinary Institute, have also transferred this technology to veterinarian medicine to cope with virus mutations during animal migration and breeding. Their research reduces risks of disease transmission among livestock.

SSI members have also led the investigation of new biomarkers for clinical diagnosis. Using only blood samples, Feng Gao, Chunfang Gao, and Jian Hou have enabled early detection of liver cancer and blood cancer, based on the investigation of such new biomarkers, which could provide information for timely interventions. Xiangjun Chen is studying the mechanisms of how neural autoimmune diseases are developed, and the strategies for an accurate, early diagnosis. Dajin Li is investigating the role of immune molecules in reproduction medicine, which are crucial to a healthy pregnancy and early fetal development. Yuejuan Zheng is working on traditional Chinese medicine regulation of immune function on tumours and infectious diseases.

“Looking back at SSI’s 40-year history and our diverse achievements, we have never stopped this pursuit of collaborative excellence, bringing together a wealth of talent and achievements,” says Tongxin Chen. “We look forward to strengthening scientific ties to spearhead new directions in immunological research.”