Nature: scientists have developed a new generation of car-t cells that are resistant to "fatigue" state to successfully resist solid tumors

December 10, 2019 / BIOON / -- recently, an international magazine Nature In the report above, scientists from Stanford University Medical Center developed a new method through research, which may reprogram car-t cells (immune cells against cancer) to extend their own activity and increase their potential to resist human cancer cells in laboratory culture and mice Photo source: cc0 public domain gene engineering cells often feel "tired" after experiencing the initial active state, and the effective way to avoid this "tired" ability is to develop a new generation of car-t cells, which are very effective for the treatment of solid tumors But up to now, researchers are not clear about the molecular mechanism involved In this study, the researchers studied mice carrying human leukemia and bone cancer cells The researchers hope to start clinical trials on leukemia patients in the next 18 months, and eventually expand the clinical trials to solid tumor patients Crystal, MD Mackall said: 'we all know that T cells are enough to eliminate cancer, but the same T cells will also evolve into natural brakes, which will gradually reduce their response after a long period of activity Now researchers have developed a new method to slow down this "tired" response of T cells, and improve the activity of car-t cells against blood cancer and solid tumors Car-t cells, also known as chimeric antigen receptor T cells, can produce car-t cells by genetic engineering modification of patients' own T cells, which can kill cancer cells by recognizing special proteins on the surface of cancer cells In 2017, car-t cells became the star cells of global concern After that, FDA approved them for the treatment of relapsed or unresponsive acute lymphoblastic leukemia Later in the same year, another version of car-t cell therapy was also approved for the treatment of some types of lymphoma Although the response of blood cancer to car-t cell therapy is better, less than half of patients need to control their disease for a long time, usually because car-t cells are "tired", they lose the ability to constantly proliferate and resist cancer cells, overcome this "tired" state or the purpose of many years of cancer researchers to carry out a lot of research In this study, the researchers analyzed what happens when T cells are "tired" and whether they are likely to effectively inhibit the "tired" of such cells; using a new technology called ATAC SEQ, the researchers were able to identify the genomic regions of genes that are overexpressed or underexpressed in regulatory circuits When we use this technique to compare the genomes of healthy and "tired" T cells, we recognize some significant differences in gene expression patterns, especially when we find that "tired" T cells exhibit a large imbalance in gene expression activity, which can regulate the level of specific proteins in cells, thereby increasing the inhibition of their own activities Expression of sex proteins When the researchers modified car-t cells to restore their balance by overexpressing the c-jun gene, which increases the expression of proteins related to T cell activity, they found that the cells could maintain their activity and proliferate under laboratory conditions, even when the cells were "tired"; compared with conventional car-t cell therapy, the modified car-t cells were used to refine the cells In addition, car-t cells expressing c-Jun also reduced the tumor burden and prolonged the life span of laboratory mice carrying human osteosarcoma At last, the researcher said that at present, we want to know whether car-t cells can be used to help resist solid tumors Now, researchers have developed a new method to promote cells to become tolerant to "fatigue" state and improve their ability to resist solid tumors in mice Although later researchers need to conduct a lot of research to test in human body, this study has We hope to help them develop a new generation of car-t cells and improve the treatment of many human cancers Original source: Lynn, R.C., Weber, E.W., sotillo, e et al C-Jun overexpression in car T cells causes emission resistance Nature (2019) doi: 10.1038/s41586-019-1805-z