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The latest research results of the Department of Biotherapy of the PLA General Hospital were published in "Nature-Communications"
Time:2021-01-19

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On January 18, 2021, the internationally renowned academic journal Nature-Communication (impact factor 12.353) published online on Low-dose decitabine enhances CAR through epigenetic reprogramming from the Department of Biotherapy, First Medical Center, PLA General Hospital The research results of T cell anti-tumor function.

In the past 10 years, the emergence of anti-tumor immunotherapy methods represented by immune cells such as chimeric antigen receptor-modified T (CAR T) and PD-1 antibody has attracted great attention from academic circles and clinics at home and abroad, and has been in many cases. The clinical treatment of various solid tumors and hematological malignancies has been widely carried out. The Department of Biological Therapy of PLA General Hospital is the first institution in China to carry out independent research and development and clinical transformation of CAR T cell therapy technology. As early as 2013, it used this technology to treat my country’s first patient, and has since achieved a series of original clinical transformations. Results. However, how to further improve the clinical efficacy of CAR T cells and PD-1 antibodies is not only an urgent clinical need to be solved, but also a key subject of various fund applications.

In 2015, Professor Han Weidong’s team put forward a new concept of "apparent immune enhancement" based on a large number of clinical practices, and under the guidance of this theoretical system, created a low-dose decitabine sensitization potentiation PD-1 antibody anti-tumor The new clinical program successfully verified the superiority of the program in the clinical treatment of relapsed and refractory Hodgkin's lymphoma, and was published in the internationally renowned journal "Journal of Clinical Oncology" in 2019. On this basis, research is conducted on whether low-dose DNA demethylation drugs, such as decitabine, can enhance the anti-tumor efficacy of immune cells such as CAR T, and even break through the efficacy of immune cells in the treatment of solid tumors.

The project was carried out under the funding of major projects of the Natural Science Foundation of China, key projects, and two major R&D projects of the Ministry of Science and Technology. First, it studied the effects of different drug concentrations and durations of action on CAR T cells, explored appropriate drug concentrations, and further systematically The epigenetic and transcriptomic reprogramming effects of Decitabine on T cells were studied, and it was found that the anti-tumor ability of CAR T cells treated with low Citabine was increased by 30-100 times, and the expansion ability increased by 10 It can be more than doubled, and can be gathered in a large number of tumor sites, and exist in the body for a long time to monitor the recurrence and progress of tumors.

The research lasted for 3 years and was mainly completed by research and development personnel in the laboratory such as Wang Yao, associate researcher of the Department of Biological Therapy. The first author of the article is Wang Yao, and the co-first authors include Tong Chuan, Dai Hanren, and Wu Zhiqiang. The responsible corresponding author is Han Weidong. .

The research provides a new intervention approach for how to improve the anti-tumor ability of T cells. While applying for national patents, in order to promote the conversion of the research results into new clinical treatment methods as soon as possible, Professor Han Weidong’s team has applied for and registered a new clinical The test protocol is used to improve the clinical efficacy of CAR T in the treatment of hematological tumors and solid tumors.