- CAR-T is a therapy in which T-cells are removed from a patient’s body and re-engineered to make them into deadly cancer-seeking cells, which then target a particular cancer and destroy it. On a molecular level, CARs are proteins that are attached to the T-cell during the modification process. They reenter the body looking for their match—specifically the antigens (also usually proteins) on tumor cells.
- CAR-T therapies, which are currently in development for treatment of leukemia and lymphomas, are so powerful in killing cells rapidly that up to one-third of patients develop an extreme inflammatory, and sometimes fatal, response.
- Companies developing these therapies are aware of this problem. Some have been working to develop an "off-switch" which would suppress CAR-T if serious side effects occur.
While CAR-T therapies are still about three to four years away from approval, researchers are determined to address the major safety issue, which has emerged in clinical trials—and with cure rates between 40% and 90% for various blood cancers, it's well worth the effort. They are focusing on decreasing risk by building in an additional receptor on the CAR-T cell that can be controlled by adding on a second medication, such as Rituxan.
In some cases, companies are developing their own off-switch technologies—including companies such as Bellicum and Cellectis SA. In other cases, companies such as Ziopharm are developing a pipeline of off-switch therapies for companies such as Intrexon.
It's a label-intensive and capital-intensive process, but clearly investors are confident that it is well worth the effort. Shares of CAR-T companies, including bluebird bio—whose shares have risen 650% in 12 months—are skyrocketing, as the investment community sees therapies emerging that can not only treat blood cancers, but eventually solid tumors as well.