CAR-T cells express synthetic receptors that detect specific molecular markers, or antigens, on cancer cells using an antibody fragment as an external sensor. When the CAR binds its antigen to a cancer cell, its signaling modules are activated and trigger the innate cytotoxic weaponry of the T cell to destroy the tumor cell.
The authors, Melita Irving and Greta Maria Paola Giordano Attianese of the Ludwig Institute for Cancer Research recall that “CAR-T cells are already used today to treat a number of blood cancers, but significant challenges for this type of immunotherapy applied to solid tumors remain, both in terms of safety and effectiveness.” This research addresses these challenges by directly integrating on/off switches activated by already approved drugs into the design of CARs.
CAR-T cells controlled remotely
Indeed, the problem is that many solid tumor antigens are also found on healthy cells, increasing the risk of off-target effects. Thus, in the case of solid tumors, treatment with CAR-T cells can provoke destructive immune responses that are difficult to control and can even be fatal for the patient. Conversely, and perhaps more commonly, immunosuppressive conditions of the solid tumor microenvironment can push antitumor T cells, including those equipped with CARs, into the state of exhaustion.
“Having the ability to remotely activate CAR-T cells to varying degrees through the use of different doses of an activating drug and then deactivate them on demand will improve the safety of the therapy. This remote control of CAR-T cell activity could also be used to reduce T-cell exhaustion, thereby improving the durability of patient responses to immunotherapy.”
The researchers then plan to better characterize the performance of their new technology in different tumor models.
