Guideng Li, PhD | Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College; Hongcheng Cheng, PhD; Ermei Xie, MS; Yajing Qiu, MS; Jing Du, MS; Yue Xu, MS; Zhe Wang, PhD
Competition Sponsor: Chinese Academy of Medical Sciences
Awardee Year: 2024
Adoptive T cell therapy (ACT) holds significant promise for treating tumors and age-related diseases, including autoimmune disorders. The effectiveness and longevity of ACT depend largely on the differentiation state of the transferred T cells. Currently, there is a lack of cost-effective and efficient methods for inducing a low-differentiation state in T cells and achieving prolonged in vitro expansion. The project aims to develop new methods for the large-scale preparation of low-differentiated anti-tumor and anti-aging T cell products, so as to break the technical bottlenecks in the large-scale preparation of long-lasting T cell products and to promote the clinical application of universal, highly efficient, and low-cost T cells.
Our preliminary analysis of single-cell sequencing data identified a notable increase in mannose metabolism in stem-like progenitor exhausted CD8 + T cells. We also found that supplementing the culture medium with mannose promotes the differentiation of these stem-like T cells, enhancing their persistence and anti-tumor activity in vivo. Therefore, the project plans to further study the molecular mechanism of mannose metabolism regulating the stemness differentiation of T cells, and generate TIL, TCR-T, CAR-T and universal CAR-T cell products targeting tumor and autoimmune diseases through genetic engineering modification and prolonged D-mannose treatment. Additionally, the potential application of mannose in anti-aging and anti-uPAR CAR-T products will be explored.