Chinese scientists in the United States have made great achievements: reprogramming T cells to enhance cancer immune response

Chinese scientists at St Jude Children's research hospital in the United States have found a molecular "brake" that limits the effectiveness of adoptive cell therapy This new treatment strategy can enhance the effect of cancer immunotherapy, thus slowing down tumor growth and prolonging the life span of cancer mice At 2:00 on December 12, 2019 Beijing time, nature published the study This finding provides a good prospect for the development of more effective adoptive cell therapy, such as car T-cell therapy The purpose of immunotherapy is to use the tumor specific T cells of the patients themselves for anti-cancer treatment Before transfusion to patients, these T cells are collected, expanded and regulated if necessary Some patients have a good response to the treatment, but the effect of adoptive cell therapy on solid tumors is poor "Our goal is to improve the persistence of tumor specific T cells and their antitumor efficacy," said Dr Chi Hongbo, a researcher in the Department of immunology at St Jude's children's hospital Our research shows that tumor specific T cells can be reprogrammed to have better persistence and strong killing activity at the same time The results of the preclinical model of this study are exciting " Crispr-cas9 and regenase-1 researchers used crispr-cas9 technology to conduct in vivo screening experiments and identified a molecule in tumor specific T cells, namely, regenase-1 This molecule plays a role in inhibiting the anti-tumor immune response When regenase-1 was deleted, the life span, efficacy and accumulation of T cells in tumor were significantly increased Compared with the mice treated with control T cells, the mice treated with reverse-1 knockout T cells had longer life span and smaller tumor size The function of regenase-1 was previously thought to inhibit the activation of T cells "This study shows that regenase-1 also inhibits two important T cell signaling pathways," said Dr Wei Jun, of the Department of immunology at St Jude's children's hospital He and Dr long Lingyun are co authors of the study In this study, Dr Wei Jun found that the transcription factors BATF and Tcf-1 are new targets of the regenase-1 BATF promotes T cell metabolism and enhances the ability of T cell accumulation and killing tumor cells Tcf-1 prolongs T cell life "The traditional view is that these processes are mutually inhibited, and increasing the antitumor activity of T cells means that the life span of T cells is affected," Dr Wei Jun stressed But our research shows that the removal of regenase-1 can enhance the killing activity and cell life of tumor specific T cells at the same time " The combination therapy of Chi Hongbo and his research team believe that the combination therapy is a new direction of clinical cancer immunotherapy In order to further enhance the clinical application prospects of this study, they conducted a secondary screening of crispr-cas9, and found that when the signal factor PTPN2 or SOCS1 is knocked out together with regenase-1, it can further improve the effect of T-cell treatment of mouse tumors Dr Chi added: "we hope to move this research forward and explore the possibility of using regenase-1 as a new target for cancer treatment."