Heavy discovery: Super CAR-T cells completely eliminate tumors and prevent recurrence
March 07, 2018 Source: Medical Valley
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Immunotherapy has become a new hope for humans to fight cancer, in which CAR-T cell therapy is genetically engineered by the Chimeric Antigen Receptor (CAR), which recognizes tumor cell surface antigens, on T cells obtained from patients. These T cells become the cell weapon for killing tumors, and this therapy is considered to be one of the most promising treatments for cancer.
In recent years, the results of CAR-T therapy in the treatment of malignant hematological tumors are obvious to all. Currently, only two cellular immunotherapy Kymriah and Yescarta are approved for blood tumors worldwide. However, using CAR-T The treatment of solid tumors is not so successful, in part because the molecules it targets are present on the surface of normal cells and cancer cells, leading to serious side effects, which requires scientists to consider target antigen selection, toxicity management, and immunity. Inhibition of the regulation of the tumor microenvironment, etc., therefore, for scientists, the treatment of solid tumors is still a huge test.
Recently, the latest issue of Nature-Biotechnology published a powerful article on immunotherapy of tumors. A team of scientists from Japan prepared the IL-17 and CCL-19 genes by transferring them into CAR-T cells. "Super CAR-T cells" capable of effectively killing tumors, in a variety of solid tumor mouse models, the "super CAR-T cells" achieve complete elimination of tumors for solid tumors that are almost ineffective in conventional CAR-T.
In the experiment, scientists also called this "super CAR-T cell" as "7 × 19 CAR-T". According to previous studies, reticular fibroblasts in lymphoid tissue can secrete chemokines IL7 and CCR19. Among them, CCR19 can recruit peripheral T cells and DC cells (dendritic cells) into lymphoid tissues, and IL7 can promote T cell proliferation while maintaining T cell stability. The researchers are inspired by this, and it is expected that IL-17 and CCL19 will also be loaded. Go to CAR-T cells to see if you can recruit more T cells and DC cells to treat tumors together to kill tumors together.
In fact, the researchers also achieved their goal. In the experiment, the researchers used modified 7x19 CAR-T cells to treat tumors in mice, then sliced ​​the tumor tissue and used immunofluorescence to observe tumor tissue. The number of T cells and DC cells showed that after treatment with 7x19 CAR-T cells, T cells and DC cells increased significantly, while mice treated with conventional CAR-T had few T cells and DC cells in tumor tissues. Both are on the outer edge of the tumor tissue. This indicates that 7x19 CAR-T cells can help T cells and DC cells in the body to effectively enter the solid tumor tissue, thereby killing the tumor cells.
The final test results are surprising. Mice with mast cells pretreated with cyclophosphamide pretreated with conventional CAR-T or 7x19 CAR-T, respectively, found that conventional CAR-T can only slightly improve mast cells. Survival of tumor mice, the general survival rate is 30%, and 7x19 CAR-T cell treatment can completely eliminate the tumor of all experimental mice, and the survival rate is almost 100%.
In addition to mast cell carcinoma, the researchers also tested lung adenocarcinoma and pancreatic cancer, which were essentially or completely ineffective in conventional CAR-T therapy. In experiments with lung adenocarcinoma mice and pancreatic cancer mouse models, 7x19CAR- T cell therapy also achieved complete elimination of tumor tissue in lung adenocarcinoma mice, and achieved long-term inhibition of tumors in pancreatic cancer mice, significantly prolonging the survival of mice.
At the same time, the researchers also found that mice treated with 7x19 CAR-T cells produced a large number of cancer memory T cells in the body, which can effectively prevent cancer recurrence. It is manifested that even after using the new generation of CAR-T for 100 days, it is impossible to form a tumor in mice by inoculation of cancer cells.
In addition, the researchers also found that the use of IL-7 alone and CCL19 alone can not effectively improve the killing ability of CAR-T, only IL-7 and CCL19 can simultaneously exert the maximum tumor killing effect.
Original search:
"IL-7 and CCL19 expression in CAR-T cells improved immune cell infiltration and CAR-T cell survival in the tumor"
Operation Lamp,Wireless Ent Surgical Headlight,Surgical Dental Veterinary Head-Bend Led Light,Portable Led Shadowless Lamp
Medton Medical , https://www.medtonmedical.com